Survivin-induced Aurora-B kinase activation: A mechanism by which APC mutations contribute to increased mitoses during colon cancer development.

ABSTRACT: APC mutations initiate most colorectal cancers (CRCs), but cellular mechanisms linking this to CRC pathology are unclear. We reported that wild-type APC in the colon down-regulates the anti-apoptotic protein survivin, and APC mutation up-regulates it, explaining why most CRCs display survivin overexpression and apoptosis inhibition. However, it does not explain another hallmark of CRC pathology--increased mitotic figures and cell proliferation. Because survivin activates aurora-B kinase (ABK) in vitro, catalyzing mitosis, we hypothesized that in normal colonic crypts, APC controls ABK activity, while in neoplastic APC-mutant crypts, ABK activity is up-regulated, increasing mitosis. We quantitatively mapped intracryptal distributions of survivin, ABK, and markers of activated downstream sig

SUBMITTER: Zhang T 

PROVIDER: S-EPMC2993266 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature