| First Author | Shin KJ | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 577 |
| Pages | 103-109 | PubMed ID | 34509721 |
| Mgi Jnum | J:312405 | Mgi Id | MGI:6788767 |
| Doi | 10.1016/j.bbrc.2021.09.012 | Citation | Shin KJ, et al. (2021) Phospholipase Cgamma1 represses colorectal cancer growth by inhibiting the Wnt/beta-catenin signaling axis. Biochem Biophys Res Commun 577:103-109 |
| abstractText | As essential phospholipid signaling regulators, phospholipase C (PLC)s are activated by various extracellular ligands and mediate intracellular signal transduction. PLCgamma1 is involved in regulating various cancer cell functions. However, the precise in vivo link between PLCgamma1 and cancer behavior remains undefined. To investigate the role of PLCgamma1 in colorectal carcinogenesis, we generated an intestinal tissue-specific Plcg1 knock out (KO) in adenomatous polyposis coli (Apc) (Min/+) mice. Plcg1 deficiency in Apc(Min/+) mice showed earlier death, with a higher colorectal tumor incidence in both number and size than in wild-type mice. Mechanistically, inhibition of PLCgamma1 increased the levels of its substrate phosphoinositol 4,5-bisphosphate (PIP2) at the plasma membrane and promoted the activation of Wnt receptor low-density lipoprotein receptor-related protein 6 (LRP6) by glycogen synthase kinase 3beta (GSK3beta) to enhance beta-catenin signaling. Enhanced cell proliferation and Wnt/beta-catenin signaling were observed in colon tumors from Plcg1 KO mice. Furthermore, low PLCgamma1 expression was associated with a poor prognosis of colon cancer patients. Collectively, we demonstrated the role of PLCgamma1 in vivo as a tumor suppressor relationship between the regulation of the PIP2 level and Wnt/beta-catenin-dependent intestinal tumor formation. |
