RRC ID 44303
Author Hori M, Miki T, Okamoto M, Yazama F, Konishi H, Kaneko H, Shimamoto F, Ota T, Temme A, Tatsuka M.
Title The detergent-soluble cytoplasmic pool of survivin suppresses anoikis and its expression is associated with metastatic disease of human colon cancer.
Journal PLoS One
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.
Volume 8(2)
Pages e55710
Published 2013-1-1
DOI 10.1371/journal.pone.0055710
PII PONE-D-12-21517
PMID 23405201
PMC PMC3565976
MeSH Animals Anoikis / physiology* Apoptosis* Blotting, Western CHO Cells Cell Proliferation Cells, Cultured Colon / metabolism Colorectal Neoplasms / metabolism Colorectal Neoplasms / pathology* Cricetinae Cytoplasm / metabolism* Detergents / pharmacology* ErbB Receptors / metabolism Fluorescent Antibody Technique Humans I-kappa B Proteins / metabolism Immunoprecipitation Inhibitor of Apoptosis Proteins / metabolism* NF-KappaB Inhibitor alpha NF-kappa B / metabolism Neoplasm Invasiveness Neoplasm Metastasis Rectum / metabolism Survivin X-Linked Inhibitor of Apoptosis Protein / metabolism
IF 2.74
Times Cited 12
Human and Animal Cells 8505C(RCB2103)