Breast Cancer Stem Cells Survive Periods of Farnesyl-Transferase Inhibitor-Induced Dormancy by Undergoing AutophagyReport as inadecuate




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Bone Marrow ResearchVolume 2011 2011, Article ID 362938, 7 pages

Research Article

The Laboratory of Cytoskeletal Physiology, Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA

The Center For Translational Cancer Research, University of Delaware, 320 Wolf Hall, Newark, DE 19716, USA

Received 15 February 2011; Accepted 18 May 2011

Academic Editor: Ross Brown

Copyright © 2011 Moumita Chaterjee and Kenneth L. van Golen. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A cancer stem cell has been defined as a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. These tumor-forming cells could hypothetically originate from stem, progenitor, or differentiated cells. Previously, we have shown that breast cancer cells with low metastatic potential can be induced into a reversible state of dormancy by farnesyl transferase inhibitors FTIs. Dormancy was induced by changes in RhoA and RhoC GTPases. Specifically, RhoA was found to be hypoactivated while RhoC was hyperactivated. In the current study we demonstrate that these dormant cells also express certain known stem cell markers such as aldehyde dehydrogenase I ALDHI and cluster of differentiation 44 CD44. We also show that autophagy markers Atg5, Atg12, and LC3-B are expressed in these dormant stem cell-like breast cancer cells. Inhibiting autophagy by inhibitor 3-methyladenine 3-MA blocked the process of autophagy reversing the dormant phenotype. Further, we show that c-jun NH2 terminal kinase JNK-SAPK is upregulated in these dormant stem cell-like breast cancer cells and is responsible for increasing autophagy.





Author: Moumita Chaterjee and Kenneth L. van Golen

Source: https://www.hindawi.com/



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