Wnt pathway-independent activities of the APC tumor suppressor

Jenifer R. Prosperi, Kathleen H. Goss

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations

Abstract

The adenomatous polyposis coli (APC) tumor suppressor gene is commonly lost in both inherited and sporadic colorectal cancer and is frequently inactivated in many other human cancers. Moreover, Apc deficiency in animal models is sufficient for tumorigenesis in a diverse set of tissue types, demonstrating that APC loss not only correlates with cancer pathogenesis but drives tumor development. Over the last two decades since its identification, much attention has been devoted to deciphering the molecular mechanisms responsible for APC?s tumor suppressor activity. The picture that is emerging is one of APC as a 'gatekeeper' of epithelial and tissue homeostasis by serving as a scaffold for multi-protein complexes, including the ?-catenin destruction machinery. Although regulation of Wnt signaling by APC through ?-catenin degradation has been well studied, separable Wnt-independent functions of APC have been identified. In this review, we will summarize the interaction of APC with junctional and polarity complexes, the cytoskeleton, nuclear proteins and apoptotic factors. Emerging evidence will be presented that supports the importance of these interactions in apical-basal and front-rear polarity, migration, differentiation, DNA replication, mitosis, DNA repair and apoptosis through Wnt pathway-independent mechanisms. The contribution of these processes to tumor development as a result of APC inactivation will be discussed. Lastly, we will address how the uncoupling of these activities from Wnt signaling may provide a therapeutic opportunity for treating APC-deficient cancers. Together, these generally under-appreciated, Wnt-independent aspects of APC function may significantly revise the accepted view of APC-mediated tumor suppression and, importantly, uncover novel strategies for cancer treatment.

Original languageEnglish (US)
Title of host publicationTumor Suppressors
PublisherNova Science Publishers, Inc.
Pages105-132
Number of pages28
ISBN (Print)9781617619861
StatePublished - Jan 1 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Prosperi, J. R., & Goss, K. H. (2011). Wnt pathway-independent activities of the APC tumor suppressor. In Tumor Suppressors (pp. 105-132). Nova Science Publishers, Inc..