Search

Breast cancer is the most common malignant tumor in women and the main cancer causing death in females. Breast cancer therefore seriously threatens women's health and life span. Although there are a variety of comprehensive and multidisciplinary treatments for different types of breast cancer, the overall prognosis of advanced breast cancer remains unsatisfactory. The incidence of breast cancer is increasing year by year, and the age of onset is gradually decreasing, making the discovery of a breakthrough in breast cancer treatment a major problem that needs to be solved urgently. A large number of studies have shown the growth of breast cancer cells can be inhibited by inducing ferroptosis. Acid sphingomyelinase has also been confirmed to be involved in cell death induced by ferroptotic agonists. This article reviews the progress in the use of acid sphingomyelinase and ferroptosis in the treatment of breast cancer, and summarizes the mechanism of ferroptosis in breast cancer cells and its correlation with acid sphingomyelinase. This review will provide a theoretical foundation for seeking new therapeutic targets for breast cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: The novel centrosomal regulatory protein Sec23 homolog B (SEC23B) regulates autophagy in cells, thereby providing energy and nutrients that contribute to tumor growth and distant metastasis. However, whether this role is involved in the mechanism of infiltrative metastasis in breast cancer is unclear. The aim of this study was to investigate the molecular mechanism by which SEC23B promotes breast cancer infiltration and metastasis. Methods: The association between SEC23B expression and breast cancer prognosis and metastasis was analyzed using Kaplan-Meier Plotter database and HCMDB database. MCF-7 cells were divided into vector group (control) and SEC23B overexpression plasmid group (SEC23B), and MDA231-LM2 cells were divided into SEC23B knockdown group (sh-SEC23B) and control group (sh-NC). Western blot was used to detect the expressions of SEC23B, autophagy-associated proteins [dead bone fragment 1 (SQSTM1, p62), microtubule-associated-protein light-chain-3 (LC3)] and extracellular-regulated protein kinases (ERK)/mammalian target of rapamycin (mTOR) pathway proteins in breast cancer cells. Cell migration was assessed by transwell assay and wound healing assay, and autophagic granules in cells were detected by immunofluorescence staining. In addition, an in vivo intraperitoneal tumor model was constructed to study the effect of SEC23B on breast cancer cell metastasis in vivo. Results: The overall survival of breast cancer patients with high SEC23B expression was significantly shorter than that of patients with low SEC23B expression. The expression of SEC23B in metastatic breast cancer was significantly higher than that in breast cancer without metastasis. SEC23B protein levels were lower in primary breast cancer cells (MCF-7, BT-549, MDA-MB-468 and MDA-MB-453) than in metastatic breast cancer cells (MDA231- LM2 and ZR-75-30). Compared with the control group, the SEC23B group significantly accelerated cell migration (P<0.001). Compared with the sh-NC group, the sh-SEC23B group significantly reduced cell migration (P<0.001). Compared with the control group, the expression level of LC3A/B and the formation of autophagy particles in the SEC23B group were significantly increased, while the expression of p62 protein and the phosphorylation levels of mTOR and ERK were decreased. Compared with the sh-NC group, the LC3A/B expression level and the formation of autophagy particles were significantly decreased in the sh-SEC23B group, and the phosphorylation levels of mTOR and ERK were increased, especially under starvation conditions. In in vivo experiments, tumor weight was significantly lower in the sh-SEC23B group compared with the sh-NC group (P<0.01), and there was an increase in necrotic tissue and a decrease in tumor metastasis in lung tissue in mice. sh-SEC23B group mice had a significantly lower number of lung metastatic tumors and LC3 immunohistochemical staining than the sh-NC group (P<0.01). Conclusions: SEC23B induces breast cancer autophagy and promotes cancer cell metastasis by inhibiting ERK/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Background and purpose: Breast cancer is the most common malignancy in women, and it is also the cancer with the highest number of new cases worldwide in 2020. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for approximately 20% of all breast cancers, which indicates higher rate of recurrence and metastasis and a poor prognosis. Therefore, it is of great significance to explore the biomarkers related to HER2-positive breast cancer. This study aimed to investigate the expression of circ-0003910 in HER2-positive breast cancer tissues and cells, and to clarify the effect of circ-0003910 on the migration and invasion of breast cancer cells. Methods: Circular RNA (circRNA) microarray was used to screen circRNA differentially expressed in HER2-positive breast cancer cells, and significantly overexpressed circRNA was selected as the research target. Fluorescence in situ hybridization (FISH) assay was used to detect the subcellular localization of circ-0003910. BaseScope assay was used to analyze the expression and clinical significance of circ-0003910 in breast cancer tissues. Circ-0003910 overexpressed and knockdown breast cancer cells were constructed by transfection of cloned plasmid and siRNA in vitro. The effect of circ-0003910 on the migration and invasion ability of breast cancer cells was detected by transwell assay. The molecular mechanism of circ0003910 promoting the migration and invasion of breast cancer cells was preliminarily explored by TMT quantitative proteomics techniques. Results: CircRNA microarray analysis showed that a total of 1 843 differentially expressed circRNAs were screened in HER2-positive breast cancer cells (fold change≥2, P<0.05), including 845 upregulated circRNAs and 998 downregulated circRNAs. Compared with normal breast epithelial cells, the differential expression ratio of circ-0003910 in HER2-positive breast cancer cells was 24.39. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) results showed that the expression of circ0003910 was higher in HER2-positive breast cancer cells than in other molecular types of breast cancer cells, and BaseScope assay verified that circ-0003910 was mainly located in the cytoplasm of HER2-positive breast cancer tissue cells. Overexpression of circ0003910 promoted the migration and invasion of breast cancer cells, while circ-0003910 knockdown produced the opposite effects. Proteomics identification showed that 197 proteins were changed after overexpression of circ-0003910, of which 104 proteins were upregulated and 93 proteins were downregulated. GO and KEGG enrichment analysis suggested that circ-0003910 may be involved in biological processes such as cell adhesion molecule synthesis, transcriptional dysregulation in cancer, and protein digestion and absorption. Conclusion: Circ-0003910 is upregulated in breast cancer cells and can promote the migration and invasion of breast cancer cells, which may be a new biomarker and target for the treatment of metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Bone metastasis is one of the most serious complications in advanced breast cancer patients. Severe osteodynia, pathological fracture and other complications in bone metastasis of breast cancer can seriously affect the quality of life and shorten life span. In recent years, with the further understanding of the mechanism of bone metastases and the cross-talk between tumor cells and bone microenvironment, development and application of many new effective drugs have made significant progress in the treatment of bone metastasis of breast cancer. This article reviewed the mechanism of bone metastasis of breast cancer and current treatment advances. [ABSTRACT FROM AUTHOR]