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

Citation data:

Oncotarget, ISSN: 1949-2553, Vol: 7, Issue: 43, Page: 70898-70911

Publication Year:
2016
Captures 21
Readers 21
Citations 6
Citation Indexes 6
Repository URL:
http://scholarworks.unist.ac.kr/handle/201301/20778
PMID:
27765922
DOI:
10.18632/oncotarget.12286
Author(s):
Lee, Yu Jin; Shin, Kyeong Jin; Park, Soo-Ah; Park, Kyeong Su; Park, Seorim; Heo, Kyun; Seo, Young-Kyo; Noh, Dong-Young; Ryu, Sung Ho; Suh, Pann-Ghill
Publisher(s):
Impact Journals, LLC; IMPACT JOURNALS LLC
Tags:
Medicine; GPR81; breast cancer; amphiregulin; angiogenesis; Akt
article description
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.