Page 54 - ebook

[A. Biochemistry/Molecular Biology] A-27

Phospholipase Cγ1 represses colorectal cancer growth by

inhibiting the Wnt/β-catenin signaling axis

Hyun-Jun Jang¹*

¹Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919,

Korea

As essential phospholipid signaling regulators, phospholipase C (PLC)s are activated by various extracellular ligands

and mediate intracellular signal transduction. PLCγ1 is involved in regulating various cancer cell functions. However,
the precise in vivo link between PLCγ1 and cancer behavior remains undefined. To investigate the role of PLCγ1 in

colorectal carcinogenesis, we generated an intestinal tissue-specific Plcg1 knock out (KO) in adenomatous polyposis
coli (Apc) Min/+ mice. Plcg1 deficiency in ApcMin/+ mice showed earlier death, with a higher colorectal tumor

incidence in both number and size than in wild-type mice. Mechanistically, inhibition of PLCγ1 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 3β (GSK3β) to
enhance β-catenin signaling. Enhanced cell proliferation and Wnt/β-catenin signaling were observed in colon tumors

from Plcg1 KO mice. Furthermore, low PLCγ1 expression was associated with a poor prognosis of colon cancer
patients. Collectively, we demonstrated the role of PLCγ1 in vivo as a tumor suppressor relationship between the

regulation of the PIP2 level and Wnt/β-catenin-dependent intestinal tumor formation. the National Research
Foundation of Korea (NRF) grant funded by the Korea government (2020R1I1A1A01074940)