Rakesh, Kumar and Aswathy, Mary Paul and Ravikumar, Amjesh and Bijesh, George and Pillai, M. R (2020) Coordinated dysregulation of cancer progression by the HER familyand p21-activated kinases. Cancer metastasis reviews, 39. pp. 583-601. ISSN 1573-7233

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Abstract

Most epithelial cancer types are polygenic in nature and are driven by coordinated dysregulation of multiple regulatory pathways,genes, and protein modifications. The process of coordinated regulation of cancer promoting pathways in response to extrinsicand intrinsic signals facilitates the dysregulation of several pathways with complementary functions, contributing to the hall-marks of cancer. Dysregulation and hyperactivation of cell surface human epidermal growth factor receptors (HERs) andcytoskeleton remodeling by p21-activated kinases (PAKs) are two prominent interconnected aspects of oncogenesis. We brieflydiscuss the discoveries and significant advances in the area of coordinated regulation of HERs and PAKs in the development andprogression of breast and other epithelial cancers. We also discuss how initial studies involving heregulin signalingviaHER3-HER2 axis and HER2-overexpressing breast cancer cells not only discovered a mechanistic role of PAK1 in breast cancerpathobiology but also acted as a bridge in generating a broader cancer research interest in other PAK family members and cancertypes and catalyzed establishing the role of PAKs in human cancer, at-large. In addition, growth factor stimulation of the PAKpathway also helped to recognize new facets of PAKs, connecting the PAK pathway to oncogenesis, nuclear signaling, geneexpression, mitotic progression, DNA damage response, among other phenotypic responses, and shaped the field of PAK cancerresearch. Finally, we recount some of the current limitations of HER- and PAK-directed therapeutics in counteracting acquiredtherapeutic resistance and discuss how cancer’s as a polygenic disease may be best targeted with a polygenic approach.

Item Type:	Article
Uncontrolled Keywords:	Cancer . EGFR family . PAKs . Signaling . Polygenic disease . Gene expression
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	26 Nov 2020 06:36
Last Modified:	26 Nov 2020 06:36
URI:	http://rgcb.sciencecentral.in/id/eprint/990

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