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Colorectal cancer (CRC) is the third most common cause of cancer-associated mortality worldwide. Currently, 5-fluorouracil (5-FU) remains a widely used chemotherapeutic drug in the treatment of CRC; however, 5-FU resistance during treatment has become a common problem. Livin, a member of the inhibitor of apoptosis protein family, is considered to be associated with tumor resistance to chemotherapy. In the present study, Livin-silenced cells were generated by introducing a lentivirus into HCT116 and SW620 colon cancer cell lines. Acridine orange/ethidium bromide staining was used as an indicator of cell death. Western blot analysis was performed to detect protein expression levels, and transmission electron microscopy was used to assess autophagy. The half-maximal inhibitory concentration of 5-FU in colon cancer cells was evaluated using a Cell Counting Kit-8 assay. The results of the present study confirmed that silencing Livin significantly enhanced colon cancer cell death in the presence of 5-FU, increased expression levels of various apoptosis- and autophagy-associated proteins and augmented chemotherapeutic sensitivity to 5-FU. Furthermore, the present study demonstrated that this effect may be reversed when autophagy or apoptosis was inhibited, indicating that apoptosis and autophagy were involved in this process. The protein kinase B signaling pathway and B-cell lymphoma-2 expression levels significantly decreased following Livin knockdown, suggesting they may contribute to the regulation of apoptosis and autophagy crosstalk, which caused the Livin knockdown-induced cell death observed. [ABSTRACT FROM AUTHOR]

Livin is a novel member of the inhibitor of apoptosis protein family, which has been identified to be expressed in various malignancies and is suggested to be associated with poor prognostic significance. However, no data are available concerning the significance of livin in mid‑distal rectal cancer. In the present study, livin expression, and its association with clinicopathological characteristics and prognosis was examined in patients with mid‑distal rectal cancer. Apoptotic susceptibility, invasion capacity and chemosensitivity of LoVo cells were investigated using small interfering RNA (siRNA)‑mediated knockdown of livin. It was revealed that livin was highly expressed in mid‑distal rectal cancer tissues compared with the normal rectal mucosal tissues. Livin expression was associated with pathological grade, extent of invasion (T stage) and extent of lymph node metastasis (N stage) of tumor, contributing to poor prognosis of mid‑distal rectal cancer following surgery. The data suggest that aggressive surgery should be applied in patients with mid‑distal rectal cancer with high expression of livin. It was also revealed that knockdown of livin by siRNA increased the apoptotic rate, suppressed invasion of LoVo cells, and decreased the half‑maximal inhibitory concentration of oxaliplatin and 5‑fluorouracil by ~50% in LoVo cells significantly compared with control groups. The data suggested that a combination of downregulation of livin and anticancer drugs may significantly decrease the toxicity of anticancer drugs. Taken together, the present study indicated that livin may be a promising target in clinical therapy of mid‑distal rectal cancer. [ABSTRACT FROM AUTHOR]

Although gene therapy has brought new insights into the treatment of malignant melanoma, targeting delivery of nucleic acid which targets critical oncogene/anti-oncogene in vivo is still a bottleneck in the therapeutic application. Our previous in vitro studies have found that the oncogene Livin could serve as a potential molecular target by small interfering RNA for gene therapy of malignant melanoma. However, how to transport Livin small interfering RNA into malignant melanoma cells specifically and efficiently in vivo needs further investigation. Cumulative evidence has suggested that single-chain antibody-mediated small interfering RNA targeted delivery is an effective way to silence specific genes in human cancer cells. Indeed, this study designed a protamine-single-chain antibody fusion protein, anti-MM scFv-tP, to deliver Livin small interfering RNA into LiBr cells. Further experiments confirmed the induction of cell apoptosis and suppression of cell proliferation by anti-MM scFv-tP in LiBr cells, along with efficient silence of Livin gene both in vitro and in vivo. Altogether, our findings provide a feasible approach to transport Livin small interfering RNA to malignant melanoma cells which would be a new therapeutic strategy for combating malignant melanoma. [ABSTRACT FROM AUTHOR]

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Livin is a novel member of the inhibitors of apoptosis protein family and has been implicated in the development and progression of colorectal cancer (CRC). However, the underlying mechanisms of Livin in CRC remain not fully understood. In this study, we investigated the effects of Livin expression on the proliferation and metastasis of CRC cells and also addressed its related molecular mechanism to metastasis. The expression of Livin in CRC cells (HCT116, SW480, and HT-29 cell lines) was determined by Western blot analysis. Our results show that the overexpression of Livin significantly promotes the proliferation, migration, and invasion of SW480 cells. Concurrently, the inhibition of Livin reduces the proliferation, migration, and invasion of HCT116 cells. In addition, Livin overexpression promotes the epithelial- mesenchymal transition, as evidenced by a decrease in epithelial E-cadherin expression and an increase in mesenchymal markers, including vimentin, Slug, and Snail. Furthermore, adding the NF-κB inhibitor, BAY 11-7028, or transfecting with small interfering RNA against p65 notably restores the expression level of E-cadherin and attenuates the invasive ability of Livinoverexpressing cells. Taken together, these results indicate that Livin potentiates migration and invasion of CRC cells partially through the induction of epithelial-mesenchymal transition via NF-κB activation. Livin may be a potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the effect of temozolomide (TMZ) on the antiapoptotic gene livin and the associated gene caspase-3. Cancer stem cells were isolated from U251 glioblastoma cells using immunomagnetic beads. The glioma cells and glioma stem cells were transfected with livin or small hairpin RNA (shRNA) against livin using lentiviral vectors. Quantitative PCR, flow cytometry and a Cell Counting kit-8 assay were used to detect the expression of livin and caspase-3, analyze the cell cycle and investigate cell proliferation, respectively, following treatment with various concentrations of TMZ (0, 25, 50, 100, 200 and 400 µmol/l) for different periods of time (24, 48 and 72 h). The expression levels of livin and caspase-3 in the U251 stem cells were significantly higher than those in the U251 cells (P<0.01). At the same intervention time, the expression levels of livin decreased and those of caspase-3 increased as the concentration of TMZ increased (P<0.05). The expression levels of livin and caspase-3 in the U251 cells were lower than those in the U251 stem cells with the same intervention time and concentration of TMZ (P<0.05). The cell cycle was arrested in the G2/M phase in the U251 cells following TMZ intervention; the proportion of cells in the G2/M phase increased as the concentration of TMZ increased (P<0.05). The U251 stem cells were arrested in the S phase following treatment with TMZ; the proportion of cells in the S phase increased as the concentration of TMZ increased (P<0.05). In conclusion, the expression levels of livin and caspase-3 were effectively inhibited and increased, respectively, in all cell models following treatment with TMZ. TMZ is able to arrest the cell cycle and enhance cell apoptosis. U251 stem cells are less vulnerable than U251 cells to TMZ. [ABSTRACT FROM AUTHOR]

Livin, a member of the inhibitor of apoptosis proteins has been considered to be a poor prognostic marker in malignancies. However, little is known about the clinical relevance of livin expression in childhood acute lymphoblastic leukemia (ALL). The aim of the present study was to assess the expression of livin on leukemic blasts of de novo childhood ALL and its relevance to clinical and hematological findings, and treatment outcome. The expression of livin was analyzed in 80 patients with newly diagnosed childhood ALL using quantitative reverse transcriptase-polymerase chain reaction. The results of the study revealed that the expression levels of livin were higher in patients with favorable prognostic factors. Furthermore, livin expression was associated with a favorable early response to chemotherapy (leukemic blast <25 % day 7 bone marrow response) ( P = 0.001). Patients with high livin expression were associated with significantly higher CR rate ( P = 0.02) and lower mortality rate ( P = 0.05) than those with low livin expression. Kaplan-Meier curves demonstrated that high livin expression was associated with significantly longer DFS ( P = 0.004) and overall survival ( P = 0.02). Multivariate analysis demonstrated that livin expression was independent favorable prognostic factor for OS and DFS ( P = 0.05 and P = 0.01, respectively). This study suggests that livin expression could be a novel prognostic marker in childhood ALL thus it could be incorporated into patient stratification and treatment protocols. [ABSTRACT FROM AUTHOR]

The antiapoptotic factor Livin has been considered critical for tumor progression and poor prognosis for variant types of tumors. However, there are only limited reports regarding its expression and biological functions in colon cancer. Here, we examined Livin expression in four colon cancer cell lines (HCT116, RKO, KM12C, and SW620) in the presence or absence of cisplatin that was used as a model reagent. We found the different response to cisplatin was related to endogenous Livin expression level. From among a panel of apoptosis-related factors (p53, Bcl-2, Bcl-XL, BAX, and survivin), the expression of Livin was upregulated after cisplatin treatment in a dose-dependent manner. Both immunocytochemistry and nuclear cytoplasmic fractionation indicated Livin remained in the cytoplasm after treatment with cisplatin. In an attempt to explore the mechanism, we found the elevated expression of Livin was not due to the decreased degradation by proteosome but was enhanced at the mRNA level. Besides, cisplatin treatment activated the mammalian target of rapamycin (mTOR) pathway as shown by increased phosphorylation of Akt1, mTOR, S6K, and 4E-BP1, together with the elevated Livin. The PI3K inhibitor LY294002 inhibited both the phosphorylation of mTOR and upregulation of Livin. The stable overexpression of Livin inhibited the activation of caspase-3 and led to resistance to cisplatin, while the knockdown of Livin by siRNA rendered colon cancer cells more sensitive to cisplatin. Our study, along with others, highlighted the potential of Livin for cancer therapy in colon cancer. [ABSTRACT FROM AUTHOR]

Therapeutic targeting of melanoma antigens frequently focuses on the melanocyte differentiation or cancer-testis families. Antigen-loss variants can often result, as these antigens are not critical for tumor cell survival. Exploration of functionally relevant targets has been limited. The melanoma inhibitor of apoptosis protein (ML-IAP; livin) is overexpressed in melanoma, contributing to disease progression and treatment resistance. Improved understanding of the significance of ML-IAP immune responses in patients has possible therapeutic applications. We found ML-IAP frequently expressed in melanoma metastases by immunohistochemistry. To assess spontaneous immunity to ML-IAP, an overlapping peptide library representing full-length protein was utilized to screen cellular responses in stage I-IV patients and healthy controls by ELISPOT. A broad array of CD4 and CD8 cellular responses against ML-IAP was observed with novel class I and class II epitopes identified. Specific HLA-A*0201 epitopes were analyzed further for frequency of reactivity. The generation of specific CD4 and cytotoxic T cells revealed potent functional capability including cytokine responsiveness to melanoma cell lines and tumor cell killing. In addition, recombinant ML-IAP protein used in an ELISA demonstrated high titer antibody responses in a subset of patients. Several melanoma patients who received CTLA-4 blockade with ipilimumab developed augmented humoral immune responses to ML-IAP as a function of treatment which was associated with beneficial clinical outcomes. High frequency immune responses in melanoma patients, associations with favorable treatment outcomes, and its essential role in melanoma pathogenesis support the development of ML-IAP as a disease marker and therapeutic target. [ABSTRACT FROM AUTHOR]

Objective: The inhibitor of apoptosis protein (IAP) livin is frequently overexpressed in melanoma. Livin binds caspases and thereby inhibits apoptosis. We found that caspases cleave livin to produce a truncated form with a paradoxical proapoptotic activity. Methods: We assessed the correlation of livin expression with survival among 114 melanoma patients treated with an autologous melanoma vaccine. In 52 patients, resection resulted in no evidence of disease (NED) and 62 remained with active disease (WAD). Protein levels were assessed using Western blot. Results: We found livin protein expression in 44/114 samples (38.4%). Median overall survival was 1.4 years in NED patients with high levels of livin protein, 8.4 years in those with low-intermediate levels and not reached in patients who did not express livin (p = 0.025). The corresponding overall survival was 2.3 years among WAD patients with high levels of livin protein, 11.3 years in those with low-intermediate levels and, paradoxically, only 4.0 years in patients who did not express livin (p = 0.012). Conclusion: Livin protein expression may play a role in the progression of melanoma and correlates with survival. A high level of the protein is associated with a poor prognosis. However, in WAD patients low to intermediate level of livin, rather than absence of the protein, is associated with a favorable prognosis. This is probably due to the paradoxical proapoptotic activity of this important regulator of apoptosis. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Livin, a novel member of the human inhibitors of apoptosis protein family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. The present study was designed to investigate the potential of using RNA interference (RNAi) technique to downregulate Livin expression, and the subsequent effect on human glioma cells. The results showed that knockdown of Livin expression by short interfering RNA (siRNA) significantly inhibited glioma cell proliferation and increased cell apoptosis through cell arrest in the G/G phase of cell cycle in vitro. Furthermore, Livin siRNA significantly suppressed tumor growth in nude mice. Together, these findings suggest that RNAi-mediated downregulation of Livin expression could lead to potent antitumor activity in glioma cells and might serve as a novel therapeutic strategy in clinic. [ABSTRACT FROM AUTHOR]

Livin is a member of the inhibitors of apoptosis (IAP) family, which plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Abnormal Livin expression is sometimes detected during the process of cancer formation and/or progression. Thus, Livin research may provide an opportunity for the development of potential therapy for Livin-relevant cancers. In this review, we introduce Livin structure, biological function, and its role in cancer formation and progression and the possible interventions for cancer therapy. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to test the expressions of Livin and insulin-like growth factor II (IGF-II) in colorectal cancers and discuss their significance of carcinogenesis and progression in colorectal cancers, to provide a new target and theory basement for cancer therapy. Methods: The expressions of Livin and IGF-II were detected by immunohistochemistry SABC in 60 cases of colorectal cancer and their associated colorectal tissues, and the associations between the expression levels of Livin and IGF-II and clinical pathological characteristics were analyzed. Results: The positive rates of Livin and IGF-II in colorectal carcinomas were 68.33% and 63.33% respectively, higher than those of para-carcinomatous normal tissues and colorectal adenomas. There were no significant correlations between the expressions of Livin, IGF-II in colorectal carcinomas and the patient's age, sex, tumor size and location, while distant metastasis, Dukes stage, histological type, lymph node metastasis, and whether the tumors have received radiotherapy and chemotherapy were significantly correlated with the expressions of Livin, IGF-II in colorectal carcinomas. Conclusion: Livin and IGF-II play important roles in carcinogenesis and progression of colorectal cancer. This study showed obvious correlation between the expressions of Livin and IGF-II in colorectal cancers. It could be used as the reference for further researches. Livin is hopeful to be a new molecular target in cancer therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVES To assess the protein expression of Livin, an apoptosis inhibitor, in renal cell carcinoma (RCC) and to determine its prognostic relevance. PATIENTS AND METHODS Immunohistochemical staining for Livin was performed in tissue microarrays (TMAs), including tumour tissue cores, from patients with RCC who had undergone renal surgery. In 682 TMAs cytoplasmatic staining intensity and nuclear staining quantity were evaluated, and the association of Livin expression with progression-free survival (PFS) and cancer-specific survival (CSS) was analysed with a multivariate Cox regression model. RESULTS Over a median (range) follow-up of 5.2 (0–16.1) years, 204 patients (28%) had died from their disease. The CSS rates at 1 and 5 years for the entire cohort was 88% and 71%. Cytoplasmatic Livin staining was absent in 516 (76%) specimens; staining was positive in 166 (24%) specimens. Weak nuclear Livin staining (≤25%) was present in 571 (84%) specimens, strong nuclear staining (26–100%) in 111 (16%). In multivariate analysis, high (>25%) nuclear Livin expression was a favourable independent predictor of PFS and CSS even after adjusting for tumour stage, Fuhrman grade, age, sex and Karnofsky severity rating. Cytoplasmatic Livin expression did not offer additional prognostic information. CONCLUSION High nuclear Livin expression is a favourable independent predictor of PFS and CSS in patients with RCC. [ABSTRACT FROM AUTHOR]

DNA damage, chromosomal abnormalities, oncogene activation, viral infection, substrate detachment and hypoxia can all trigger apoptosis in normal cells. However, cancer cells acquire mutations that allow them to survive these threats that are part and parcel of the transformation process or that may affect the growth and dissemination of the tumor. Eventually, cancer cells accumulate further mutations that make them resistant to apoptosis mediated by standard cytotoxic chemotherapy or radiotherapy. The inhibitor of apoptosis (IAP) family members, defined by the presence of a baculovirus IAP repeat (BIR) protein domain, are key regulators of cytokinesis, apoptosis and signal transduction. Specific IAPs regulate either cell division, caspase activity or survival pathways mediated through binding to their BIR domains, and/or through their ubiquitin-ligase RING domain activity. These protein–protein interactions and post-translational modifications are the subject of intense investigations that shed light on how these proteins contribute to oncogenesis and resistance to therapy. In the past several years, we have seen multiple approaches of IAP antagonism enter the clinic, and the rewards of such strategies are about to reap benefit. Significantly, small molecule pan-IAP antagonists that mimic an endogenous inhibitor of the IAPs, called Smac, have demonstrated an unexpected ability to sensitize cancer cells to tumor necrosis factor-α and to promote autocrine or paracrine production of this cytokine by the tumor cell and possibly, other cells too. This review will focus on these and other developmental therapeutics that target the IAPs in cancer.Oncogene (2008) 27, 6252–6275; doi:10.1038/onc.2008.302 [ABSTRACT FROM AUTHOR]

The inhibitor of apoptosis family member livin is expressed in several neoplasms but is absent in most benign tissues. Livin has therefore been evaluated as a diagnostic and prognostic marker and recently gained much attention as a target for tumor therapy. We evaluated the expression of livin splicing variants in 131 testicular germ cell tumors (TGCT) compared to 20 normal testicular tissue samples using dual-color real-time RT-PCR and Western blot analysis. Expression of livin β was detected in 51.9% and expression of the α-variant in 28.2% of the TGCT specimens. None of the splicing variants could be detected in normal testicular tissue. Livin α was only expressed in combination with the β-isoform, the respective expression levels being highly intercorrelated (Spearman’s correlation coefficient: ρ = 0.854). Livin expression was strongly related to TGCT differentiation but not to clinical tumor stage and patient age. The β-variant was expressed in 67.5% of seminomas but only in 27.1% of nonseminomatous germ cell tumors (NSGCT). Expression of the α-variant was detected in 38.5% of seminomas and in 10.4% of NSGCT. Among NSGCT, livin expression was confined to embryonal carcinomas (EC) and mixed NSGCT exclusively consisting of EC and seminoma elements. Our findings suggest livin to be implicated in testicular tumorigenesis and to be related to the histological TGCT subtype. Considering that livin expression is restricted to malignant testicular tissue, it appears reasonable to conduct further investigations regarding its targeted inhibition in TGCT. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To investigate the inhibitory effects of LMWH suppressing the expression of Livin and inducing the apoptosis of the osteosarcoma cells. Osteosarcoma cells line MG-63 was cultured in vitro. MTT assay and flow cytometry were used to study the effect of LMWH with different concentration suppressed the prolifetation and induced apoptosis in osteosarcoma cells line MG-63. The expression of Livin of osteosarcoma cells line MG-63 was analysed by the immunohistochemistrical method and PT-PCR. Low molecular weight heparin could inhibit the growth of osteosarcoma cell line MG-63. With the LMWH’s increasing, the apoptosis rate was increased significantly. Immunohistochemistrical method and PT-PCR showed that the expression of Livin of osteosarcoma cells line MG-63 declined obviously than that before medication. LMWH has very strong anti-tumor effect in vitro. The possible mechanisms of LMWH anti-tumor effect are associate with the effect of suppressing the expression of Livin and inducing cell apoptosis. [ABSTRACT FROM AUTHOR]

Livin is a member of the Inhibitor of Apoptosis Protein family which inhibits apoptosis induced by a variety of stimuli. We previously identified Livin and demonstrated that following apoptotic stimuli, Livin is cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity. In the present study, we reveal that while full-length Livin shows diffuse cytoplasmic localization, truncated Livin (tLivin) is found in a peri-nuclear distribution with marked localization to the Golgi apparatus. Using mutation analysis, we identified two domains that are crucial for the pro-apoptotic activity of tLivin: the N-terminal region of tLivin which is exposed by cleavage, and the RING domain. We demonstrate that, of the N-terminal sequence, only the first N-terminal glycine residue dictates the peri-nuclear distribution of tLivin. However, while the perinuclear localization of tLivin is essential, it is not sufficient for tLivin to exert its pro-apoptotic function. Once tLivin is properly localized, an intact RING domain enables its pro-apoptotic function. [ABSTRACT FROM AUTHOR]

Livin has recently been identified as a member of the inhibitor of apoptosis family expressed in several types of cancer but not in most benign tissues. Expression levels of livin were associated with prognosis in various malignancies, but livin expression and its prognostic relevance have not been evaluated in renal cell carcinomas (RCC). In a cohort of 152 RCC patients, we analyzed the relative expression of livin and its splicing variants by real-time RT-PCR and Western blot in tumor and adjacent normal renal tissue specimens. Livin expression was detected in 59 (38.8%) of 152 RCC specimens but in none of the normal samples. Both splicing variants were present in the livin-positive RCC specimens. Livin expression levels did not correlate with pathological or clinical parameters and were not predictive of patient outcome. Our findings suggest that livin expression in RCC is not of prognostic relevance. Further studies to clarify the role of livin expression in RCC and its potential value as a target for immune-mediated tumor destruction are warranted. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Livin (alternatively called ML-IAP or KIAP) is a cancer-associated member of the antiapoptotic inhibitor of apoptosis protein family. Two splicing variants of Livin, designated Livin α and Livin β, have been identified. The significance of these isoforms for Livin-mediated apoptosis inhibition is largely unclear. Using an isoform-specific RNA interference (RNAi) strategy, we silenced endogenous Livin expression in HeLa cells. We found that the targeted inhibition of Livin β, but not of Livin α, blocked the growth of HeLa cells in clonogenic survival assays. In addition, silencing of Livin β, but not of Livin α, sensitized HeLa cells to different proapoptotic stimuli such as UV irradiation, tumor necrosis factor α, or etoposide. These events were linked to activation of caspase-3 and increased poly(ADP-ribose) polymerase cleavage, specifically upon silencing of Livin β. The proapoptotic sensitization of HeLa cells upon RNAi-mediated silencing of the endogenous livin gene was specifically reverted by ectopic expression of Livin β but not of Livin α. We conclude that the Livin β isoform plays the key role for the antiapoptotic protection of HeLa cells by the livin gene. Our results show that the Livin isoforms can strongly differ in their functional significance for the antiapoptotic resistance of tumor cells. Studies evaluating Livin as a novel diagnostic and prognostic tumor marker should benefit from isoform-specific expression analyses. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor suppressor 53 (p53) is a multifunctional protein that regulates cell cycle, DNA repair, apoptosis and metabolic pathways. In colorectal cancer (CRC), mutations of the gene occur in 60% of patients and are associated with a more aggressive tumor phenotype and resistance to anti-cancer therapy. In addition, inhibitor of apoptosis (IAP) proteins are distinguished biomarkers overexpressed in CRC that impact on a diverse set of signaling pathways associated with the regulation of apoptosis/autophagy, cell migration, cell cycle and DNA damage response. As these mechanisms are further firmly controlled by p53, a transcriptional and post-translational regulation of IAPs by p53 is expected to occur in cancer cells. Here, we aim to review the molecular regulatory mechanisms between IAPs and p53 and discuss the therapeutic potential of targeting their interrelationship by multimodal treatment options. Despite recent advances in the treatment of colorectal cancer (CRC), patient's individual response and clinical follow-up vary considerably with tumor intrinsic factors to contribute to an enhanced malignancy and therapy resistance. Among these markers, upregulation of members of the inhibitor of apoptosis protein (IAP) family effects on tumorigenesis and radiation- and chemo-resistance by multiple pathways, covering a hampered induction of apoptosis/autophagy, regulation of cell cycle progression and DNA damage response. These mechanisms are tightly controlled by the tumor suppressor p53 and thus transcriptional and post-translational regulation of IAPs by p53 is expected to occur in malignant cells. By this, cellular IAP1/2, X-linked IAP, Survivin, BRUCE and LIVIN expression/activity, as well as their intracellular localization is controlled by p53 in a direct or indirect manner via modulating a multitude of mechanisms. These cover, among others, transcriptional repression and the signal transducer and activator of transcription (STAT)3 pathway. In addition, p53 mutations contribute to deregulated IAP expression and resistance to therapy. This review aims at highlighting the mechanistic and clinical importance of IAP regulation by p53 in CRC and describing potential therapeutic strategies based on this interrelationship. [ABSTRACT FROM AUTHOR]