Multiple roles of APC and its therapeutic implications in colorectal cancer

L Zhang, JW Shay - JNCI: Journal of the National Cancer …, 2017 - academic.oup.com
JNCI: Journal of the National Cancer Institute, 2017academic.oup.com
Adenomatous polyposis coli (APC) is widely accepted as a tumor suppressor gene highly
mutated in colorectal cancers (CRC). Mutation and inactivation of this gene is a key and
early event almost uniquely observed in colorectal tumorigenesis. Alterations in the APC
gene generate truncated gene products, leading to activation of the Wnt signaling pathway
and deregulation of multiple other cellular processes. It has been a mystery why most
patients with CRC retain a truncated APC protein, but accumulating evidence suggest that …
Abstract
Adenomatous polyposis coli (APC) is widely accepted as a tumor suppressor gene highly mutated in colorectal cancers (CRC). Mutation and inactivation of this gene is a key and early event almost uniquely observed in colorectal tumorigenesis. Alterations in the APC gene generate truncated gene products, leading to activation of the Wnt signaling pathway and deregulation of multiple other cellular processes. It has been a mystery why most patients with CRC retain a truncated APC protein, but accumulating evidence suggest that these C terminally truncated APC proteins may have gain of function properties beyond the well-established loss of tumor suppressive function. Here, we will review the evidence for both the loss of function and the gain of function of APC truncations and how together they contribute to CRC initiation and progression.
Oxford University Press