Adaptive phenotypic switching in breast cancer in response to matrix deprivation

Sundararaman, A and Kumar, S and Rangarajan, A (2020) Adaptive phenotypic switching in breast cancer in response to matrix deprivation. [Book Chapter]

PDF phe_swi_imp_651-676_2020.pdf - Published Version Restricted to Registered users only Download (581kB) | Request a copy

Abstract

Cancer cells spread to distant organs by a multistep process termed metastasis, which involves cell-detachment from the extracellular matrix, entry and transit through the vasculature, exit into distant organs followed by reestablishment of a new tumor. Cancer cells acquire several unique properties by employing divergent molecular phenotypes to negotiate this complex multistep metastasis cascade. Matrix deprivation causes a dramatic rearrangement of the cytoskeleton. This triggers an apoptotic cell-death program, called anoikis, in most normal cells. However, a subpopulation of cancer cells overcome this barrier and survive in anchorage-deprived conditions, and subsequently contribute to the metastatic growth. Matrix deprivation triggers short- and long-term adaptive responses in cancer cells that enable their phenotype switching. The ability to reversibly adapt to matrix deprivation is one fundamental prerequisite for metastasis. One mechanism by which matrix deprivation is sensed by cells is through an increase in calcium and ROS flux that causes a switch in the metabolic phenotype of cells through the regulation of the key energy sensor, AMP-activated protein kinase (AMPK), which in turn regulates another kinase protein kinase B/PKB (Akt). The resultant bistable metabolic phenotype between adherent and matrix-deprived cell states is governed by a double negative feedback loop between AMPK and Akt. In addition to metabolic plasticity and adaptation, matrix deprivation also switches on the epithelial-to-mesenchymal transition and stemness programs that contribute to phenotypic plasticity. These interrelated regulatory circuits confer better fitness for cancer cells to adapt to anchorage deprivation. We will explore specific examples of how matrix deprivation induces adaptive and reversible phenotypic switching during cancer progression. © 2020 Elsevier Inc.

Item Type:	Book Chapter
Publication:	Phenotypic Switching: Implications in Biology and Medicine
Publisher:	Elsevier
Additional Information:	The copyright for this article belongs to Elsevier.
Keywords:	AMPK; Anchorage independence; Anoikis; Anoikis resistance; ECM; Matrix deprivation; Metabolism; Plasticity
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	07 Feb 2023 04:09
Last Modified:	07 Feb 2023 04:09
URI:	https://eprints.iisc.ac.in/id/eprint/79968

Actions (login required)

View Item