CANCER

Negative Reinforcement

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Science  28 Mar 2014:
Vol. 343, Issue 6178, pp. 1405
DOI: 10.1126/science.343.6178.1405-b
CREDIT: M. E. FEIGIN ET AL., PNAS 111, 11 (5 MARCH 2014) © 2014 NATIONAL ACADEMY OF SCIENCES

About 15 to 20% of breast cancers are classified as “triple negative,” so called because these tumors do not express three key proteins that are biomarkers and/or drug targets for breast cancer: the estrogen receptor, the progesterone receptor, and HER2 (a member of the epidermal growth factor receptor family). Triple-negative tumors are aggressive and more likely to metastasize than other breast cancers, and there is no effective treatment. To acquire new insights into the biology and possible therapy of these tumors, Feigin et al. looked for aberrant expression of G protein–coupled receptors, cell signaling proteins that have been successfully targeted for treatment of other disorders such as depression. An orphan receptor called GPR161 was found to be overexpressed in triple-negative but not in other breast cancer types. In cell culture, high expression levels of GPR161 induced proliferation of mammary epithelial cells, disrupted the acinar structures formed by these cells, and enhanced their invasive capacity. GPR161 was shown to activate the mTORC1/S6K signaling pathway. These observations suggest that GPR161 dysfunction contributes to the development of triple-negative breast cancers.

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1320239111 (2014).

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