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Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent malignancy with a 5-year survival rate of 54%. Therefore, disease management improvement is required. The present study aimed to assess the role of caveolin-1 (Cav-1) in the metastasis of head and neck tumor cells. Short hairpin RNA was used to silence Cav-1 expression in Tu686 cells. Proliferation, migration, invasion, morphology and the levels of effector proteins were assessed in cells. Upon Cav-1 silencing, E-cadherin levels were decreased, while vimentin levels were significantly increased. Cell migration, quantified by wound healing and Transwell assays, was significantly increased. Meanwhile, Cav-1 and transforming growth factor β1 (TGF-β1) receptor were identified to be co-localized. In addition, Cav-1-knockdown resulted in increased phosphorylation of SMAD family member 2 (P<0.05), a downstream effector of TGF-β signaling. In addition, there was a mutual regulation, with increasing TGF-β1 levels leading to a dose-dependent decrease of Cav-1 expression levels (P<0.05). These findings indicate that Cav-1 inhibits cell metastasis in HNSCC, suggesting the involvement of the TGF-β signaling pathway. [ABSTRACT FROM AUTHOR]

Caveolae-mediated endocytosis regulates cell adhesion and growth in an anchorage-dependent manner. Studies of the endocytic function of caveolae have suggested a wide-ranging list of cargoes, including a number of receptors and extracellular proteins, ligands and nutrients from the extracellular matrix. Disruption of the processes of caveolae-mediated endocytosis mediated by signaling proteins is critical to cellular integrity. Caveolin-1 and dynamin-2 are the 2 major proteins associated with endocytotic function. Mechanistically, dynamin-2 has a co-equal role with caveolin-1 in terms of caveolae-derived endosome formation. Recent studies have revealed the pathological outcomes associated with the dysregulation of caveolin-1 and dynamin-2 expression. Increased expression levels of the gene for caveolin, Cav-1, resulting in augmented cellular metastasis and invasion, have been demonstrated in various types of cancer, and overexpression of the gene for dynamin-2, DNM2, has been associated with tumorigenesis in cervical, pancreatic and lung cancer. An increased expression of Cav-1 and DNM2 is known to be associated with the invasive behavior of cancer cells, and with cancer progression. Furthermore, it has been previously demonstrated that, in caveolar assembly and caveolae mediated endocytosis, Cav-1 interacts directly with DNM2 during the processes. Altered expression of the 2 genes is critical for the normal function of the cell. The expression patterns of Cav-1 and DNM2 have been previously examined in bladder cancer cell lines, and were each demonstrated to be overexpressed. In the present study, the expression levels of these 2 genes in bladder cancer samples were quantified. The gene expression levels of Cav-1 and DNM2 were identified to be increased 8.88- and 8.62-fold, respectively, in tumors compared with the normal controls. Furthermore, high-grade tumors exhibited significantly increased expression levels of Cav-1 and DNM2 (both P<0.0001) compared with the low-grade tumors. In addition, compared with normal control samples, the expression of the 2 genes in tumor samples was observed to be highly significant (P<0.0001), with a marked positive correlation identified for the tumors (Pearson's correlation coefficient, r=0.80 for the tumor samples vs. r=0.32 in the normal control samples). Taken together, the results of the present study demonstrated that the overexpression of Cav-1 and DNM2 genes, and a determination of their correlation coefficients, may be a potential risk factor for bladder cancer, in addition to other clinical factors. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common type of primary brain tumour in adults, and presents a very low survival rate. Isocitrate dehydrogenase (IDH)1/2 mutations have been found in ~12% of glioblastomas and are associated with long-term GBM survival. However, the risk factors that influence the prognosis of IDH-wild type GBM remain unclear. Hypoxia-inducible factor (HIF)-1α, an important oxygen-regulated transcription factor, has been demonstrated to serve a crucial role in tumour development and to be associated with a poor prognosis. In addition, caveolin-1 (CAV1) is a plasma membrane organizing protein, the expression of which can also be regulated by a hypoxic microenvironment. The present study therefore aimed to examine the expression levels of HIF-1α and CAV1, and their association with GBM prognosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to analyse the expression levels of HIF-1α and CAV1 in paired GBM tumour and adjacent non-tumour tissues. Immunohistochemistry was used to analyse the expression of the two proteins in paraffin-embedded tissues obtained from 42 patients with IDH-wild type GBM. Statistical analyses were performed to examine the correlation between HIF-1α and CAV1 expression and patient prognosis. The results revealed hat the expression levels of HIF-1α and CAV1 were upregulated in IDH-wild type GBM tissues compared to their paired non-tumour tissues (P<0.001). The expression of CAV1 was significantly correlated with high HIF-1α expression (P<0.01). In addition, overexpression of HIF-1α and CAV1 was markedly associated with a poor prognosis (P<0.001). In conclusion, HIF-1α and CAV1 may represent potential biomarkers for IDH-wild type GBM prognosis and potential targets for the development of therapies extending GBM survival. [ABSTRACT FROM AUTHOR]

There are markers of metabolic coupling in breast cancer. Loss of caveolin-1 (Cav-1) and upregulation of monocarboxylate transporters (MCTs), especially MCT1 and MCT4, serve an important role in metabolic coupling necessary for release and uptake of metabolites. However, the occurrence of these phenomena in phyllodes tumors (PTs) of the breast is unclear. A total of 101 PTs (60 benign, 26 borderline and 15 malignant) and nine breast tissue samples with no pathological lesions were analyzed. Immunohistochemical staining for Cav-1, MCT1 and MCT4 was performed using tissue microarray and their expression in both stromal and epithelial components was assessed. Cav-1 expression in PTs demonstrated a significant decrease in the stromal component compared with that in the normal breast tissues (P<0.001). MCT1 expression in both epithelial and stromal components was significantly increased in PTs, compared with that in normal breast tissues (both P<0.001). Stromal MCT1 and MCT4 expression were different depending on tumor grade of PTs, and stromal MCT1 expression significantly increased with increasing tumor grade (P<0.001). Although not statistically significant, stromal Cav-1 expression notably decreased with increases in PT grade. High stromal MCT1 expression was significantly associated with lower disease-free survival rate in comparison with low stromal MCT1 expression (P<0.05). These results suggested that changes in protein expression of Cav-1, MCT1 and MCT4 may be associated with tumorigenesis and progression of PTs of the breast. [ABSTRACT FROM AUTHOR]

Potassium voltage‑gated channel subfamily A member 5 (KCNA5) is a voltage‑gated potassium channel protein encoded by the KCNA5 gene. A large number of studies have shown that KCNA5 is associated with the survival of malignant tumors, including breast cancer, but the detailed mechanism remains inconclusive. Our previous study found that KCNA5 is co‑expressed with a scaffolding protein, caveolin‑1 in MCF‑10A‑neoT non‑tumorigenic epithelial cell. In the present study, KCNA5 and caveolin‑1 were expressed in breast cancer tissues and cell lines. Exposing MCF‑10A‑neoT to 2 mM of methyl‑β‑cyclodextrin, an agent to disrupt caveolae and lipid rafts led to a downregulation of caveolin‑1 that reduced the expression of KCNA5. Furthermore, following caveolin‑1 knockdown, the expression of KCNA5 was decreased in MDA‑MB‑231 human breast cancer and MCF‑10A‑neoT non‑tumorigenic epithelial cell lines. In subsequent experiments, the MTT assay showed that increased caveolin‑1 and KCNA5 expression promoted the survival of MCF‑7 human breast cancer cells, but cell survival was not affected following KCNA5 overexpression alone. Using small interfering RNA technology, KCNA5‑silenced MCF‑10A‑neoT cells were established and a decreased level of phosphorylated‑AKT serine/threonine kinase (AKT) was observed in the cells compared with the parental cells. Overall, these results suggested that caveolin‑1 facilitated KCNA5 expression and may be associated with AKT activation. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, and it is often observed to overexpress epidermal growth factor receptor (EGFR). Previous research has indicated that EH domain‑containing 1 (EHD1) is associated with EGFR‑mediated endocytotic recycling in multiple tumor types. The objective of the present study was to determine the protein expression levels and clinical significance of EHD1, EGFR, caveolin‑1 (CAV‑1) and RAB11 family interacting protein 3 (RAB11FIP3) in PTC. PTC specimens were analyzed for EHD1, EGFR, CAV‑1 and RAB11FIP3 expression via immunohistochemistry and western blotting. The associations between protein expression and clinicopathological features were assessed. EHD1, EGFR, CAV‑1 and RAB11FIP3 expression levels were increased in human PTC. Additionally, the expression level of EHD1 protein was significantly associated with tumor size, lymph node metastasis and EGFR expression (P<0.05). CAV‑1 was associated with tumor size and EGFR expression (P<0.05). EGFR was only associated with lymph node metastasis (P=0.027) and RAB11FIP3 was not associated with any clinicopathological characteristics. The correlations between EHD1 and EGFR (r=0.564, P<0.05), CAV‑1 (r=0.865, P<0.01) and RAB11FIP3 (r=0.504, P<0.05) were statistically significant. Overall, EHD1, CAV‑1 and RAB11FIP3, which are key proteins in endocytotic recycling, promote PTC tumorigenesis through the regulation of the transport of EGFR. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that caveolin‑1 (Cav‑1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav‑1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav‑1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan‑Meier estimator curves and the log‑rank test. Stromal Cav‑1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav‑1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav‑1 and not associated with stromal Cav‑1 expression in breast cancer samples; however, low expression of stromal Cav‑1 was negatively associated with cytoplasmic Cav‑1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav‑1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER‑2)(‑), HER‑2(+) and ER(‑) groups, the use of combined markers was more effective prognostic marker. Stromal Cav‑1 has a tumor suppressor function, and the combined marker stromal Cav‑1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav‑1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR‑mediated initiation of mitosis. [ABSTRACT FROM AUTHOR]

Caveolin-1 is a scaffold protein of caveolae in the mucosa of the gastrointestinal tract and acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. Caveolin-1 stabilizes cell-cell and cellmatrix contacts and is a hallmark of a number of different types of human cancer, including gastric cancer. All-trans retinoic acid (ATRA), a derivative of vitamin A, has been demonstrated to exhibit tumor inhibitory effects in acute leukemia and certain types of solid tumor. In the present study, treatment with ATRA was demonstrated to inhibit the proliferation of gastric cancer cell line SGC7901, in a time- and dose-dependent manner. The markedly increased membrane localization of caveolin-1 was observed in the cells that were treated with 10 µmol/l ATRA for > 48 h. In addition, it was observed that treatment with ATRA was able to regulate the level of phosphorylation of extracellular signal-regulated kinase (ERK). Therefore, the SGC7901 cells were treated with a specific agonist of ERK/mitogenactivated protein kinase (MAPK) investigate whether ATRA mediated its effects via the ERK/MAPK signaling pathway. The results of the present study demonstrated that ATRAinduced increase in membrane localization of caveolin-1 was reversed by treatment with a specific agonist of ERK/MAPK. Together, these results suggest that ATRA exhibits antigastric cancer effects. ATRA may regulate the membrane localization of caveolin-1 in order to inhibit the proliferation of SGC7901 cells. These effects of ATRA may be mediated by inhibiting the activation of ERK/MAPK signaling pathway. These results contribute to the current knowledge on the potential use of ATRA as therapy for solid tumors and provide further insight into the potential molecular mechanisms of ATRA action. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common type of cancer in men and women. Chemotherapy is an important treatment strategy for patients with terminal stage cancer. However, the development of drug resistance hampers the effectiveness of chemotherapy. Therefore, an effective therapeutic approach to target chemoresistance-associated cellular molecules is required. In the present study, drug-resistant human colorectal cancer HCT116 cells were developed by treating HCT116 cells with increasing concentrations of 5-fluorouracil (5-FU). The present study indicated that the drug-resistance cells (DRC) were resistant to 5-FU compared with parental HCT116 cells by detecting cell survival using an MTT assay. Additionally, the expression of the chemoresistance-associated protein caveolin-1 (Cav-1) was assessed by reverse transcription-quantitative polymerase chain reaction and western blotting. The results revealed that the Cav-1 expression level was significantly higher in DRC compared with that in the parental HCT116 cells. Next, Cav-1 was silenced by small interfering RNA (siRNA) or was inhibited with its specific inhibitor methyl β-cyclodextrin (MCD). MTT assay demonstrated that Cav-1 siRNA and MCD resensitized DRC to 5-FU. These data reveal that Cav-1 was involved in the development of resistance, suggesting that Cav-1 is a potential target for the treatment of colorectal cancer chemoresistance. In addition, 5-FU combined with Cav-1 siRNA or its specific inhibitor may increase the effectiveness of the treatment strategy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the expression and functions of Forkhead box protein M1 (FoxM1), Caveolin-1 (Cav-1) and E-cadherin in colorectal cancer (CRC), and to determine the correlations among these proteins in CRC development and progression. The protein expression of FoxM1, Cav-1 and E-cadherin was identified using a human CRC and normal tissue microarray. A standard immunohistochemistry assay was performed employing anti-FoxM1, anti-Cav-1 and anti-E-cadherin antibodies. The clinicopathological significance of FoxM1, Cav-1 and E-cadherin in CRC was determined, and correlations were investigated between FoxM1 and Cav-1, FoxM1 and E-cadherin, Cav-1 and E-cadherin, respectively. The level of FoxM1, Cav-1 and E-Cadherin protein expression in CRC was found to be associated with pathological grade, tumor clinical stages and the presence of metastasis, respectively. Elevated expression of FoxM1 and Cav-1 was observed in the CRC tissues, and a significant correlation was found between the two proteins in CRC. However, it was also observed that FoxM1 was overexpressed while E-cadherin expression was low, indicating that there was a negative correlation between FoxM1 expression and E-cadherin expression. Moreover, there was also a negative correlation between Cav-1 and E-cadherin expression. Overall, the elevated expression of FoxM1 and Cav-1 in a human CRC microarray provided novel clinical evidence to elucidate the fact that they may play a critical role in the development and progression of CRC by negatively regulating E-cadherin expression. Furthermore, the positive correlation between FoxM1 and Cav-1 suggested that the proteins may constitute a novel signaling pathway in human CRC. [ABSTRACT FROM AUTHOR]

The present study aimed to identify the role of caveolin-1 (CAV1) in hypopharyngeal squamous cell carcinoma (HSCC) and identify its possible correlation with tumor clinical parameters. Expression of CAV1 was measured using immunohistochemical staining of 66 HSCC samples and 44 samples from morphologically normal tissues adjacent to the carcinomas. Expression of CAV1 in HSCC and paracancerous tissues were 71.2 and 9.5% respectively. Levels of CAV1 expression were significantly associated with tumor differentiation, tumor-node-metastasis stage and lymph nodes metastasis (P<0.05). The present study identified that expression of CAV1 in HSCC is significantly higher than in paracancerous tissues, suggesting that this high expression of CAV1 is associated with tumor invasion and metastasis. [ABSTRACT FROM AUTHOR]

Caveolin-1 (Cav), a primary protein component of caveolae, is overexpressed in prostate cancer, thereby promoting growth and metastasis of this tumor. By contrast, pigment epithelium-derived factor (PEDF) has been shown to inhibit tumor growth and metastasis, including that of prostate cancer, via its anti-angiogenic and anti-inflammatory effects. Although it was recently demonstrated that PEDF binds to Cav and blocks its pro-inflammatory actions in endothelial cells, it remains unclear whether PEDF also inhibits the tumor-promoting effects of Cav in cultured prostate cancer cells. The present study examined the effects of PEDF on cell growth, in addition to the gene expression of interleukin-8 (IL-8), which is involved in prostate cancer progression, in the PC-3 human prostate cancer cell line. Exogenous Cav led to a dose-dependent upregulation of the mRNA expression of IL-8 in PC-3 cells, which was blocked by treatment with 1 or 10 nM PEDF, or following the overexpression of small interfering RNAs directed against Cav. Cav (10 nM) increased DNA synthesis in PC-3 cel ls, which was again suppressed by the administration of 10 nM PEDF. The results of the present study indicated that PEDF may inhibit Cav-induced increases in IL-8 gene expression and proliferation of PC-3 cells. Therefore, the suppressive effects of PEDF in prostate cancer may, in part, be ascribed to its inhibitory actions on Cav. [ABSTRACT FROM AUTHOR]

Caveolin-1 (Cav-1) is found predominately in terminally differentiated cells, such as adipocytes, endothelia and smooth muscle cells, as well as type I pneumocytes. As a main structural component of caveolae, Cav-1 is important in modulating cellular signaling. In the present study, the expression and clinical role of Cav-1 were analyzed in tumor stromal and human cancer cells, respectively. The results of previous studies have shown that the downregulation of tumor stromal Cav-1 promotes tumor survival and predicts a poor tumor prognosis, predominantly concentrating on the mechanism of the metabolism of the cancer microenvironment (according to the autophagic tumor stroma model of cancer metabolism and the reverse Warburg effect). However, contradictory results concerning the expression, clinical roles and associated mechanisms of Cav-1 have been reported. An improved understanding of Cav-1 expression in tumor stromal and cancer cells will increase knowledge with regard to the clinical value of Cav-1 and its detailed mechanisms. This review summarizes the novel data concerning the clinical values and probable mechanisms of Cav-1 expression in tumor stromal (predominantly in cancer-associated fibroblasts) and cancer cells, respectively. [ABSTRACT FROM AUTHOR]

Advanced prostate cancer is difficult to treat due to androgen resistance, its deep location and blood tumor barriers. Low-frequency ultrasound (LFU) has potential clinical applications in the treatment of prostate cancer due to its strong penetrability and high sensitivity towards tumor cells. Simvastatin has often been administered as a preventive agent in prostate tumors. The aim of the present study was to investigate the enhanced effects of LFU and microbubbles in combination with simvastatin, in inhibiting cell viability and promoting apoptosis of androgen-independent prostatic DU145 cells. Cultured DU145 cells were divided into six groups based on the combination of treatments as follows: Control, LFU, LFU and microbubbles (LFUM), simvastatin, LFU and simvastatin, LFUM and simvastatin. The cells were treated by LFU (80 kHz) continuously for 30 sec with an ultrasound intensity of 0.45 W/cm2 and a microbubble density of 20%. Simvastatin was added 30 h prior to the ultrasound exposure. The results indicated that cell viability was marginally reduced in the LFU and simvastatin alone treatment groups compared with the control 24 h following ultrasound exposure. The combination of LFU, with microbubbles or simvastatin, potentiated the growth inhibition; the greatest inhibition was observed in the cells that were subject to treatment with LFUM and simvastatin in combination. Furthermore, this inhibitory effect was enhanced in a time-dependent manner. For cell apoptosis, a low dose of simvastatin had no apparent affect on the DU145 cells, while LFU marginally promoted cell apoptosis. Microbubbles or simvastatin increased the apoptosis rate of the DU145 cells, however, the combination of LFUM and simvastatin induced a strong synergistic effect on cell apoptosis. Western blotting analysis demonstrated a high expression level of caveolin-1 in resting DU145 cells. LFUM or combined LFU and simvastatin resulted in a greater reduction in the expression compared with the control group (P<0.05). The expression of caveolin-1 was lowest in the LFUM combined with simvastatin treatment group. The expression of phospho-Akt (p-Akt) was consistent with caveolin-1, with the lowest expression levels of p-Akt observed in the cells that were treated with the combination of LFUM and simvastatin. The results indicate that LFUM in combination with simvastatin may additively or synergisti-cally inhibit cell viability and induce apoptosis of DU145 cells by downregulating caveolin-1 and p-Akt protein expression. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most lethal malignant diseases with the poorest prognosis and is the fourth leading cause of tumor-associated mortality in the industrialized world. microRNAs (miRNAs or miRs) are small noncoding RNAs of approximately 22 nucleotides long that are able to function as oncogenes or tumor suppressors in human cancer. In our study, overexpression of miR-203 in Panc-1 cells is sufficient to reduce migratory ability and invasiveness, and to induce upregulation of epithelial markers (Snail, ZO-1 and β-catenin) followed by a decrease of mesenchymal marker expression (Zeb-1, vimentin and fibronectin). We also found that the caveolin-1 mRNA or protein levels are modulated by miR-203 in Panc-1 cells. We found that exogenous miR-203 altered the level of cell migration and invasion, and the expression of associated proteins following caveolin-1 knockdown by small interfering RNA. These results demonstrate that miR-203 inhibits cell migration and invasion via caveolin-1 in pancreatic cancer cells, suggest that miR-203 expression may be a useful indicator of the metastatic potential and provide a new therapeutic target in this common malignancy. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common type of cancer in men and women. Chemotherapy is an important treatment strategy for patients with terminal stage cancer. However, the development of drug resistance hampers the effectiveness of chemotherapy. Therefore, an effective therapeutic approach to target chemoresistance-associated cellular molecules is required. In the present study, drug-resistant human colorectal cancer HCT116 cells were developed by treating HCT116 cells with increasing concentrations of 5-fluorouracil (5-FU). The present study indicated that the drug-resistance cells (DRC) were resistant to 5-FU compared with parental HCT116 cells by detecting cell survival using an MTT assay. Additionally, the expression of the chemoresistance-associated protein caveolin-1 (Cav-1) was assessed by reverse transcription-quantitative polymerase chain reaction and western blotting. The results revealed that the Cav-1 expression level was significantly higher in DRC compared with that in the parental HCT116 cells. Next, Cav-1 was silenced by small interfering RNA (siRNA) or was inhibited with its specific inhibitor methyl β-cyclodextrin (MCD). MTT assay demonstrated that Cav-1 siRNA and MCD resensitized DRC to 5-FU. These data reveal that Cav-1 was involved in the development of resistance, suggesting that Cav-1 is a potential target for the treatment of colorectal cancer chemoresistance. In addition, 5-FU combined with Cav-1 siRNA or its specific inhibitor may increase the effectiveness of the treatment strategy.

The present study aimed to identify the role of caveolin-1 (CAV1) in hypopharyngeal squamous cell carcinoma (HSCC) and identify its possible correlation with tumor clinical parameters. Expression of CAV1 was measured using immunohistochemical staining of 66 HSCC samples and 44 samples from morphologically normal tissues adjacent to the carcinomas. Expression of CAV1 in HSCC and paracancerous tissues were 71.2 and 9.5% respectively. Levels of CAV1 expression were significantly associated with tumor differentiation, tumor-node-metastasis stage and lymph nodes metastasis (P<0.05). The present study identified that expression of CAV1 in HSCC is significantly higher than in paracancerous tissues, suggesting that this high expression of CAV1 is associated with tumor invasion and metastasis.

The aim of the present study was to investigate the expression and functions of Forkhead box protein M1 (FoxM1), Caveolin-1 (Cav-1) and E-cadherin in colorectal cancer (CRC), and to determine the correlations among these proteins in CRC development and progression. The protein expression of FoxM1, Cav-1 and E-cadherin was identified using a human CRC and normal tissue microarray. A standard immunohistochemistry assay was performed employing anti-FoxM1, anti-Cav-1 and anti-E-cadherin antibodies. The clinicopathological significance of FoxM1, Cav-1 and E-cadherin in CRC was determined, and correlations were investigated between FoxM1 and Cav-1, FoxM1 and E-cadherin, Cav-1 and E-cadherin, respectively. The level of FoxM1, Cav-1 and E-Cadherin protein expression in CRC was found to be associated with pathological grade, tumor clinical stages and the presence of metastasis, respectively. Elevated expression of FoxM1 and Cav-1 was observed in the CRC tissues, and a significant correlation was found between the two proteins in CRC. However, it was also observed that FoxM1 was overexpressed while E-cadherin expression was low, indicating that there was a negative correlation between FoxM1 expression and E-cadherin expression. Moreover, there was also a negative correlation between Cav-1 and E-cadherin expression. Overall, the elevated expression of FoxM1 and Cav-1 in a human CRC microarray provided novel clinical evidence to elucidate the fact that they may play a critical role in the development and progression of CRC by negatively regulating E-cadherin expression. Furthermore, the positive correlation between FoxM1 and Cav-1 suggested that the proteins may constitute a novel signaling pathway in human CRC.

Caveolin-1 (Cav), a primary protein component of caveolae, is overexpressed in prostate cancer, thereby promoting growth and metastasis of this tumor. By contrast, pigment epithelium-derived factor (PEDF) has been shown to inhibit tumor growth and metastasis, including that of prostate cancer, via its anti-angiogenic and anti-inflammatory effects. Although it was recently demonstrated that PEDF binds to Cav and blocks its pro-inflammatory actions in endothelial cells, it remains unclear whether PEDF also inhibits the tumor-promoting effects of Cav in cultured prostate cancer cells. The present study examined the effects of PEDF on cell growth, in addition to the gene expression of interleukin-8 (IL-8), which is involved in prostate cancer progression, in the PC-3 human prostate cancer cell line. Exogenous Cav led to a dose-dependent upregulation of the mRNA expression of IL-8 in PC-3 cells, which was blocked by treatment with 1 or 10 nM PEDF, or following the overexpression of small interfering RNAs directed against Cav. Cav (10 nM) increased DNA synthesis in PC-3 cells, which was again suppressed by the administration of 10 nM PEDF. The results of the present study indicated that PEDF may inhibit Cav-induced increases in IL-8 gene expression and proliferation of PC-3 cells. Therefore, the suppressive effects of PEDF in prostate cancer may, in part, be ascribed to its inhibitory actions on Cav.

Caveolin-1 (Cav-1) is found predominately in terminally differentiated cells, such as adipocytes, endothelia and smooth muscle cells, as well as type I pneumocytes. As a main structural component of caveolae, Cav-1 is important in modulating cellular signaling. In the present study, the expression and clinical role of Cav-1 were analyzed in tumor stromal and human cancer cells, respectively. The results of previous studies have shown that the downregulation of tumor stromal Cav-1 promotes tumor survival and predicts a poor tumor prognosis, predominantly concentrating on the mechanism of the metabolism of the cancer microenvironment (according to the autophagic tumor stroma model of cancer metabolism and the reverse Warburg effect). However, contradictory results concerning the expression, clinical roles and associated mechanisms of Cav-1 have been reported. An improved understanding of Cav-1 expression in tumor stromal and cancer cells will increase knowledge with regard to the clinical value of Cav-1 and its detailed mechanisms. This review summarizes the novel data concerning the clinical values and probable mechanisms of Cav-1 expression in tumor stromal (predominantly in cancer-associated fibroblasts) and cancer cells, respectively.

Advanced prostate cancer is difficult to treat due to androgen resistance, its deep location and blood tumor barriers. Low-frequency ultrasound (LFU) has potential clinical applications in the treatment of prostate cancer due to its strong penetrability and high sensitivity towards tumor cells. Simvastatin has often been administered as a preventive agent in prostate tumors. The aim of the present study was to investigate the enhanced effects of LFU and microbubbles in combination with simvastatin, in inhibiting cell viability and promoting apoptosis of androgen-independent prostatic DU145 cells. Cultured DU145 cells were divided into six groups based on the combination of treatments as follows: Control, LFU, LFU and microbubbles (LFUM), simvastatin, LFU and simvastatin, LFUM and simvastatin. The cells were treated by LFU (80 kHz) continuously for 30 sec with an ultrasound intensity of 0.45 W/cm 2 and a microbubble density of 20%. Simvastatin was added 30 h prior to the ultrasound exposure. The results indicated that cell viability was marginally reduced in the LFU and simvastatin alone treatment groups compared with the control 24 h following ultrasound exposure. The combination of LFU, with microbubbles or simvastatin, potentiated the growth inhibition; the greatest inhibition was observed in the cells that were subject to treatment with LFUM and simvastatin in combination. Furthermore, this inhibitory effect was enhanced in a time-dependent manner. For cell apoptosis, a low dose of simvastatin had no apparent affect on the DU145 cells, while LFU marginally promoted cell apoptosis. Microbubbles or simvastatin increased the apoptosis rate of the DU145 cells, however, the combination of LFUM and simvastatin induced a strong synergistic effect on cell apoptosis. Western blotting analysis demonstrated a high expression level of caveolin-1 in resting DU145 cells. LFUM or combined LFU and simvastatin resulted in a greater reduction in the expression compared with the control group (P<0.05). The expression of caveolin-1 was lowest in the LFUM combined with simvastatin treatment group. The expression of phospho-Akt (p-Akt) was consistent with caveolin-1, with the lowest expression levels of p-Akt observed in the cells that were treated with the combination of LFUM and simvastatin. The results indicate that LFUM in combination with simvastatin may additively or synergistically inhibit cell viability and induce apoptosis of DU145 cells by downregulating caveolin-1 and p-Akt protein expression.

Pancreatic cancer is one of the most lethal malignant diseases with the poorest prognosis and is the fourth leading cause of tumor-associated mortality in the industrialized world. microRNAs (miRNAs or miRs) are small noncoding RNAs of approximately 22 nucleotides long that are able to function as oncogenes or tumor suppressors in human cancer. In our study, overexpression of miR-203 in Panc-1 cells is sufficient to reduce migratory ability and invasiveness, and to induce upregulation of epithelial markers (Snail, ZO-1 and β-catenin) followed by a decrease of mesenchymal marker expression (Zeb-1, vimentin and fibronectin). We also found that the caveolin-1 mRNA or protein levels are modulated by miR-203 in Panc-1 cells. We found that exogenous miR-203 altered the level of cell migration and invasion, and the expression of associated proteins following caveolin-1 knockdown by small interfering RNA. These results demonstrate that miR-203 inhibits cell migration and invasion via caveolin-1 in pancreatic cancer cells, suggest that miR-203 expression may be a useful indicator of the metastatic potential and provide a new therapeutic target in this common malignancy.