Defining a role for the inhibitors of apoptosis proteins in prostate cancer

McEleny, Kevin; Watson, R. William G.; Fitzpatrick, John M.

doi:10.1038/sj.pcan.4500502

Cited by 8 publications

(10 citation statements)

References 45 publications

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“…XIAP is the most potent inhibitor of caspase activity. 70,71 High expression of IAPs in cancer cells can confer resistance to TRAIL-induced apoptosis.…”

Section: Bax and Bakmentioning

confidence: 99%

Mechanisms of resistance to TRAIL-induced apoptosis in cancer

2004

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The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is regarded as a potential anticancer agent. However, considerable numbers of cancer cells, especially some highly malignant tumors, are resistant to apoptosis induction by TRAIL, and some cancer cells that were originally sensitive to TRAIL-induced apoptosis can become resistant after repeated exposure (acquired resistance). Understanding the mechanisms underlying such resistance and developing strategies to overcome it are important for the successful use of TRAIL for cancer therapy. Resistance to TRAIL can occur at different points in the signaling pathways of TRAILinduced apoptosis. Dysfunctions of the death receptors DR4 and DR5 due to mutations can lead to resistance. The adaptor protein Fas-associated death domain (FADD) and caspase-8 are essential for assembly of the death-inducing signaling complex, and defects in either of these molecules can lead to TRAIL resistance. Overexpression of cellular FADD-like interleukin-1b-converting enzymeinhibitory protein (cFLIP) correlates with TRAIL resistance in several types of cancer. Overexpression of Bcl-2 or Bcl-X L , loss of Bax or Bak function, high expression of inhibitor of apoptosis proteins, and reduced release of second mitochondria-derived activator of caspases (Smac/Diablo) from the mitochondria to the cytosol have all been reported to result in TRAIL resistance in mitochondriadependent type II cancer cells. Finally, activation of different subunits of mitogen-activated protein kinases or nuclear factor-kappa B can lead to development of either TRAIL resistance or apoptosis in certain types of cancer cells.

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“…XIAP is the most potent inhibitor of caspase activity. 70,71 High expression of IAPs in cancer cells can confer resistance to TRAIL-induced apoptosis.…”

Section: Bax and Bakmentioning

confidence: 99%

Mechanisms of resistance to TRAIL-induced apoptosis in cancer

2004

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“…Thus far, eight human IAPs have been identified including X-linked inhibitor of apoptosis protein (XIAP), inhibitor of apoptosis protein 1 (IAP1), inhibitor of apoptosis protein 2 (IAP2), and survivin (Krajewska et al, 2003). While they all appear capable of inhibiting effector caspases, IAP1 and IAP2 can directly and potently up-regulate NF-κB expression (McEleny et al, 2001). Elevated expression of all four IAPs has been shown in both animal models of prostate cancer and prostate tumors from patients undergoing prostatectomy, and this elevation appears to be present early in prostate cancer development (McEleny et al, 2001).…”

Section: Exploitation Of Apoptosis In Cancer Therapymentioning

confidence: 99%

“…While they all appear capable of inhibiting effector caspases, IAP1 and IAP2 can directly and potently up-regulate NF-κB expression (McEleny et al, 2001). Elevated expression of all four IAPs has been shown in both animal models of prostate cancer and prostate tumors from patients undergoing prostatectomy, and this elevation appears to be present early in prostate cancer development (McEleny et al, 2001). Indeed, recent evidence suggests that XIAP inhibition enhances chemotherapy sensitivity in otherwise resistant prostate cancer cell lines (Amantana et al, 2004).…”

Section: Exploitation Of Apoptosis In Cancer Therapymentioning

confidence: 99%

“…Indeed, recent evidence suggests that XIAP inhibition enhances chemotherapy sensitivity in otherwise resistant prostate cancer cell lines (Amantana et al, 2004). Another small study consisting of 23 patients revealed that expression of both IAP1 and IAP2 was dramatically up-regulated in patients receiving neoadjuvant androgen ablation, implicating IAPs in androgen independence (McEleny et al, 2001). …”

Section: Exploitation Of Apoptosis In Cancer Therapymentioning

confidence: 99%

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Targeting anoikis resistance in prostate cancer metastasis

Sakamoto

Kyprianou

2010

Molecular Aspects of Medicine

158

165

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Anoikis is a mode of apoptotic cell death, consequential to insufficient cell-matrix interactions and a critical player in tumor angiogenesis and metastasis. The events involved in tumor cell progression toward metastasis potential are mediated by integrins, which upon engagement with components of the extracellular matrix (ECM), reorganize to form adhesion complexes. Targeting apoptotic players is of immense therapeutic significance since resistance to apoptosis is not only critical in conferring therapeutic failure to standard treatment strategies, but anoikis (apoptosis upon loss of anchorage and detachment from ECM also plays an important role in angiogenesis and metastasis. The ability to survive in the absence of adhesion to the ECM, enables tumor cells to disseminate from the primary tumor site, invade a distant site and establish a metastatic lesion. Tumor cells can escape from detachment-induced apoptosis by controlling anoikis pathways, including the extrinsic death receptor pathway and the ECM-integrin mediated cell survival pathway. Considering the functional promiscuity of individual signaling effectors, it is critical to dissect the molecular networks mechanistically driving tumor cells to evade anoikis and embark on a metastatic spread. Resistance to die via anoikis dictates tumor cell survival and provides a molecular basis for therapeutic targeting of metastatic prostate cancer. Further dissection of critical anoikis signaling events will enable the therapeutic optimization of anoikis targeting to impair prostate cancer metastasis prior to its initiation. This review will discuss the molecular understanding of anoikis regulation in the tumor microenvironment and the in vivo pharmacological implementation of a novel class of antitumordrugs to optimize apoptotic-based therapeutic targeting, bypassing anoikis-resistance to impair prostate cancer progression to metastasis. Potential combination strategies targeting tumor vascularity (via anoikis) and impairing tumor initiation (via "classic" apoptosis), provide strong therapeutic promise for metastatic prostate cancer by preventing the onset of metastasis.

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“…As to PCa, several studies identified that the survivin , though not normally expressed in the normal tissue and secretory epithelial cells of the prostate [24], was strongly expressed in PCa tissues and PCa cell lines at the level of RNA or protein [25-29]. Moreover, substantial evidence indicated that overexpression of survivin was related to the established features of biologically aggressive PCa, such as Gleason score and metastases [30-32].…”

Section: Introductionmentioning

confidence: 99%

Functional promoter -31G/C variant of Survivin gene predict prostate cancer susceptibility among Chinese: a case control study

et al. 2013

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BackgroundAbnormal expression of Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin), a novel member of the inhibitor of apoptosis protein (IAP) family, has implications in many types of cancer and is considered as a new therapeutic target. We suppose that genetic variant rs9904341 in the 5′ UTR region of survivin gene may be associated with the development and progression of prostate cancer (PCa) in Chinese population.MethodsTaqMan assay method was used to genotype the polymorphism in the hospital-based case–control analysis of 665 patients with PCa and 710 age-matched cancer-free controls. The genetic associations with the occurrence and progression of PCa were calculated by logistic regression.ResultsOur results indicated that compared with GG genotypes, there was a statistically significant increased risk of PCa associated with those with CC genotypes [odds ratios (ORs) = 1.57, 95%confidence intervals (CIs) = 1.17-2.13, P = 0.004]. Moreover, stratification analysis revealed that the association was more pronounced in subgroups of nondrinkers, nonsmokers and those without a family history of cancer (all P < 0.05). In addition, we observed that PSA ≥ 20 was more frequent in patients carrying GC/CC genotypes than in those with a wild type genotype.ConclusionThe functional survivin rs9904341 genetic variant may have a substantial influence on the PCa susceptibility and evolution.

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Defining a role for the inhibitors of apoptosis proteins in prostate cancer

Cited by 8 publications

References 45 publications

Mechanisms of resistance to TRAIL-induced apoptosis in cancer

Mechanisms of resistance to TRAIL-induced apoptosis in cancer

Targeting anoikis resistance in prostate cancer metastasis

Functional promoter -31G/C variant of Survivin gene predict prostate cancer susceptibility among Chinese: a case control study

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