title: The detergent-soluble cytoplasmic pool of survivin suppresses anoikis and its expression is associated with metastatic disease of human colon cancer.
abstract: Survivin is a component of the chromosomal passenger complex (CPC) that is essential for accurate chromosome segregation. Interfering with the function of Survivin in mitosis leads to chromosome segregation errors and defective cytokinesis. Survivin contains a Baculovirus IAP Repeat (BIR) and therefore was originally classified as inhibitor of apopotosis protein (IAP), yet its role in apoptosis after cellular stress remains largely unknown. We demonstrate here, that Survivin predominantly suppresses anoikis, a form of programmed cell death induced by loss of cellular adhesion to extracellular matrix. Interestingly, cells ectopically overexpressing EGFP-Survivin showed after loss of cell-matrix-interaction a decreased expression of IκB-α. Subsequent subcellular protein fractionation and immunoprecipitation experiments revealed that XIAP interacts with detergent-soluble Survivin which is known to cooperatively activate NF-κB signaling. Examination of the expression levels of detergent soluble Survivin in colorectal cancer cell lines and in colorectal cancerous tissues revealed that detergent soluble cytoplasmic Survivin levels correlated inversely with anoikis susceptibility in colorectal cancer. Therefore, the detergent soluble cytoplasmic Survivin might be a promising predictive biomarker for lymph node and distant metastases of colorectal cancer. We conclude that an anti-apoptotic function of detergent-soluble Survivin in interphase cells experiencing anoikis is mediated at least via XIAP/IκB-α/NF-κB signaling.
authors: Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shoubara, Hiroshima, Japan.
authors: Masato
authors: M
authors: Hori
authors: Tomoharu
authors: T
authors: Miki
authors: Mayumi
authors: M
authors: Okamoto
authors: Futoshi
authors: F
authors: Yazama
authors: Hiroaki
authors: H
authors: Konishi
authors: Hiroshi
authors: H
authors: Kaneko
authors: Fumio
authors: F
authors: Shimamoto
authors: Takahide
authors: T
authors: Ota
authors: Achim
authors: A
authors: Temme
authors: Masaaki
authors: M
authors: Tatsuka
mesh_terms: D000818:Animals; D023102:Anoikis / Q000502:physiology*; D017209:Apoptosis; D015153:Blotting, Western; D016466:CHO Cells; D049109:Cell Proliferation; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012007:Rectum / Q000378:metabolism; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D003902:Detergents; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; D000072000:NF-KappaB Inhibitor alpha; C512478:EGFR protein, human; D066246:ErbB Receptors