Breast Cancer: Molecular Mechanism of SLC5A8 Inactivation…

Molecular Mechanism of SLC5A8 Inactivation in Breast Cancer.

 

Citation

Elangovan S, Pathania R, Ramachandran S, Ananth S, Padia RN, Srinivas SR, Babu E, Hawthorn L, Schoenlein PV, Boettger T, Smith SB, Prasad PD, Ganapathy V, Thangaraju M. Molecular Mechanism of SLC5A8 Inactivation in Breast Cancer. Mol Cell Biol. 2013 Oct;33(19):3920-35.

 

Abstract

SLC5A8 is a putative tumor suppressor that is inactivated in more than 10 different types of cancer, but neither the oncogenic signaling responsible for SLC5A8 inactivation nor the functional relevance of SLC5A8 loss to tumor growth has been elucidated. Here, we identify oncogenic HRAS (HRAS(G12V)) as a potent mediator of SLC5A8 silencing in human nontransformed normal mammary epithelial cell lines and in mouse mammary tumors through DNMT1. Further, we demonstrate that loss of Slc5a8 increases cancer-initiating stem cell formation and promotes mammary tumorigenesis and lung metastasis in an HRAS-driven murine model of mammary tumors. Mammary-gland-specific overexpression of Slc5a8 (mouse mammary tumor virus-Slc5a8 transgenic mice), as well as induction of endogenous Slc5a8 in mice with inhibitors of DNA methylation, protects against HRAS-driven mammary tumors. Collectively, our results provide the tumor-suppressive role of SLC5A8 and identify the oncogenic HRAS as a mediator of tumor-associated silencing of this tumor suppressor in mammary glands. These findings suggest that pharmacological approaches to reactivate SLC5A8 expression in tumor cells have potential as a novel therapeutic strategy for breast cancer treatment.

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Heather Hopkins

My work explores the relationship between the universality of myth and life as performance.

With influences as diverse as Machiavelli and Joni Mitchell, new combinations are generated from both explicit and implicit meanings.

Ever since I was a teenager I have been fascinated by the essential unreality of the zeitgeist. What starts out as yearning soon becomes corroded into a manifesto of professional courtesy, leaving only a sense of what could have been and the dawn of a new reality.

As momentary replicas become clarified through emergent and repetitive practice, the viewer is left with an epitaph for the outposts of our culture.

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Written by Heather Hopkins

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