We found GPRC5A is a potential oncogene in pancreatic ductal adenocarcinoma cells that is upregulated by gemcitabine with help from HuR1
Both GPRC5A mRNA level and protein level are upregulated in pancreatic cancer cell lines and pancreatic cancer tissue. In vitro studies of multiple pancreatic cancer cell lines showed that an increase in GPRC5A protein levels promoted pancreatic cancer cell growth and migration. Moreover, when we treated pancreatic cancer cell lines with gemcitabine, we observed an increase in GPRC5A protein abundance. On the other hand, when we knocked down GPRC5A we sensitized pancreatic cancer cells to gemcitabine.
Interestingly, upon gemcitabine stress (Step 1), HuR molecules translocate from the nucleus to the cytoplasm (Step 2). More HuR molecules are available in the cytoplasm to stabilize GPRC5A mRNA (Step 3). More GPRC5A protein is produced as a result (Step 4). GPRC5A protein enhances the pancreatic cancer cell’s resistance to gemcitabine, and stimulates the pancreatic cancer cell’s growth ability as well as migration ability (Step 5).
- Zhou, H, Telonis, AG, Jing, Y, Xia, NL, Biederman, L, Jimbo, M et al.. GPRC5A is a potential oncogene in pancreatic ductal adenocarcinoma cells that is upregulated by gemcitabine with help from HuR. Cell Death Dis. 2016;7 :e2294. doi: 10.1038/cddis.2016.169. PubMed PMID:27415424 PubMed Central PMC4973341.