oss of -catenin phosphorylation and increases its nuclear accumulation. This process is found to be independent of the PKA-cAMP pathway but rather dependent on the direct association of Gs with the -catenin destruction complex member and Rgs protein, Axin. Overexpression of the regulator of G protein binding domain of Axin, the region capable of stimulating GTPase activity and serving as a molecular scaffold, inhibits PGE2 -induced transcriptional activation of Tcf/Lef.Emerging evidence indicates a role a in primary in primary invasive ductal carcinomas of the breast. Emerging evidence indicatesfor role for EP4/Cox2 in maintaining CSC breast CSC Kundu et al. have observed have observed EP4/Cox2 in maintaining the breast the phenotype. phenotype. Kundu et al. upregulation of upregulation of both EP4 and Cox2 in a tumor-initiating cells and in metastatic and in basal-type both EP4 and Cox2 in a sub-population of sub-population of tumor-initiating cells and/or metastatic and/or not in non-metastatic or luminal-type or luminal-type cells, implicating association of EP4 cells butbasal-type cells but not in non-metastaticcells, implicating association of EP4 and Cox2 with aand Cox2 with a malignant a result, a clinically relevant EP4 antagonistEP4 antagonist malignant phenotype. As phenotype. As a result, a clinically relevant inhibits breast inhibits breast CSCs, tumorigencity in vivo. A in vivo. A number of clinical trials are CSCs, metastasis and metastasis and tumorigencity number of clinical trials are currently being currently to evaluate the to evaluate the effect of Cox2 inhibition in global targeting global OPC 8212 conducted being conductedeffect of Cox2 inhibition in cancer but such acancer but such astrategy targeting in potential cardiovascular complications that may limit its applicability. is resulting strategy is resulting in potential PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19818716 cardiovascular complications that may limit its applicability. EGFR controls a wide variety of biological processes such as proliferation, differentiation, migration and modulation of apoptosis. Aberrant receptor proliferation, differentiation, migration and modulation of apoptosis. Aberrant receptor signaling via overexpression, mutation or autocrine signaling loops has been frequently implicated in signaling via overexpression, mutation or autocrine signaling loops has been frequently implicated hyperproliferative disorders including cancer. EGFR and and its ligandsoverexpressed and in hyperproliferative disorders including cancer. EGFR its ligands are are overexpressed correlate with poor prognosis in various malignancies, including glioblastoma, breast, ovarian, gastric, and correlate with poor prognosis in various malignancies, including glioblastoma, breast, ovarian, esophageal and cervical cancers. GPCR signalingsignaling isof transactivating the EFGRthe EFGR gastric, esophageal and cervical cancers. GPCR is capable capable 
of transactivating pathway and as such, a combination combination diversity of GPCR signaling GPCR signaling with the potent pathway and as such, a of the broad of the broad diversity of with the potent signaling capacity of EFGR could serve as a paradigm for inter-receptor crosstalk. signaling capacity of EFGR could serve as a paradigm for inter-receptor crosstalk. EGFR transactivaton can proceed via several mechanisms of GPCR) EGFR transactivaton can proceed via several mechanisms . . Metalloproteases are zinc dependent endopeptidases that elicit proteolytic or activation Me
