Survivin: A molecular biomarker in cancer

Praveen Kumar Jaiswal, Apul Goel, R D Mittal, Praveen Kumar Jaiswal, Apul Goel, R D Mittal

Abstract

Survivin, a member of the inhibitor of apoptosis (IAP) protein family that inhibits caspases and blocks cell death, is highly expressed in most cancers and is associated with a poor clinical outcome. Survivin has consistently been identified by molecular profiling analysis to be associated with high tumour grade cancers, different disease survival and recurrence. Polymorphisms in the survivin gene are emerging as powerful tools to study the biology of the disease and have the potential to be used in disease prognosis and diagnosis. The survivin gene polymorphisms have also been reported to influence tumour aggressiveness as well as survival of cancer patients. The differential expression of survivin in cancer cells compared to normal tissues and its role as a nodal protein in a number of cellular pathways make it a high target for different therapeutics. This review discusses the complex circuitry of survivin in human cancers and gene variants of survivin, and highlights novel therapy that targets this important protein.

Figures

Fig. 1
Fig. 1
Structure and function of survivin protein.
Fig. 2
Fig. 2
Survivin (SVN) pathways to apoptosis. Activation of cell death pathways can be initiated through different mechanisms, including through ligand binding (FasL, TNF) to a death receptor on the cell surface (extrinsic pathway) or via direct mitochondrial signaling (intrinsic pathway). The mitochondrial pathway is initiated by activation of the Bax/Bcl-2 pathway leading to the release of apoptotic factors such as cytochrome c (cyt c) and apoptosis-inducing factor (AIF) from the mitochondrial intermembrane space into the cytoplasm. The release of cytochrome c from mitochondria results in caspase-3 activation through formation of the cytochrome c/Apaf-1(apoptotic peptidase activating factor-1)/caspase-9 apoptosome complex. Caspase-3 cleaves a number of substrates including cytoskeletal proteins and DNA. Caspase-activated DNase (CAD) and inhibitor of CAD (ICAD) initiate cleavage and fragmentation of DNA. The inhibitors of apoptosis (IAPs) inhibit cell death by physically interacting with caspases. Survivin has been shown to inhibit apoptosis through caspase-dependent and independent pathways.

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