Research Papers:

G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion

Yu Jin Lee, Kyeong Jin Shin, Soo-Ah Park, Kyeong Su Park, Seorim Park, Kyun Heo, Young-Kyo Seo, Dong-Young Noh, Sung Ho Ryu and Pann-Ghill Suh _

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Oncotarget. 2016; 7:70898-70911. https://doi.org/10.18632/oncotarget.12286

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Yu Jin Lee1, Kyeong Jin Shin1, Soo-Ah Park1, Kyeong Su Park1, Seorim Park1, Kyun Heo2, Young-Kyo Seo1, Dong-Young Noh3, Sung Ho Ryu4, Pann-Ghill Suh1

1School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea

2New Experimental Therapeutics Branch, Division of Convergence Technology, National Cancer Center, Goyang-si, Republic of Korea

3Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea

4Department of Life Science, Pohang University of Science and Technology (POSTECH), San31, Hyoja Dong, Pohang, Republic of Korea

Correspondence to:

Pann-Ghill Suh, email: [email protected]

Keywords: GPR81, breast cancer, amphiregulin, angiogenesis, Akt

Received: April 20, 2016    Accepted: September 02, 2016    Published: September 27, 2016


G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.

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