Abstract：
:GPRC5A is a G-protein-coupled receptor expressed in lung tissue but repressed in most human lung cancers. Studies in Gprc5a(-/-) mice have established its role as a tumor-suppressor function in this setting, but the basis for its role has been obscure. Here, we report that GPRC5A functions as a negative modulator of EGFR signaling. Mouse tracheal epithelial cells (MTEC) from Gprc5a(-/-) mice exhibited a relative increase in EGFR and downstream STAT3 signaling, whereas GPRC5A expression inhibited EGFR and STAT3 signaling. GPRC5A physically interacted with EGFR through its transmembrane domain, which was required for its EGFR inhibitory activity. Gprc5a(-/-) MTEC were much more susceptible to EGFR inhibitors than wild-type MTEC, suggesting their dependence on EGFR signaling for proliferation and survival. Dysregulated EGFR and STAT3 were identified in the normal epithelia of small and terminal bronchioles as well as tumors of Gprc5a(-/-) mouse lungs. Moreover, in these lungs EGFR inhibitor treatment inhibited EGFR and STAT3 activation along with cell proliferation. Finally, overexpression of ectopic GPRC5A in human non-small cell lung carcinoma cells inhibited both EGF-induced and constitutively activated EGFR signaling. Taken together, our results show how GPRC5A deficiency leads to dysregulated EGFR and STAT3 signaling and lung tumorigenesis. Cancer Res; 75(9); 1801-14. ©2015 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Zhong S,Yin H,Liao Y,Yao F,Li Q,Zhang J,Jiao H,Zhao Y,Xu D,Liu S,Song H,Gao Y,Liu J,Ma L,Pang Z,Yang R,Ding C,Sun B,Lin X,Ye X,Guo W,Han B,Zhou BP,Chin YE,Deng Jdoi
10.1158/0008-5472.CAN-14-2005subject
Has Abstractpub_date
2015-05-01 00:00:00pages
1801-14issue
9eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-14-2005journal_volume
75pub_type
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