Calpain as an effector of the Gq signaling pathway for inhibition of Wnt/β-catenin-regulated cell proliferation

Signaling pathways interact to integrate and regulate information flow in evoking complex cellular responses. We have studied the mechanisms and consequences of interactions between the Gq and Wnt/β-catenin pathways. In human colon carcinoma SW480 cells, activation of the Gq pathway inhibits β-catenin signaling as determined by transcriptional reporter and cell proliferation assays. Ca(2+) release from internal stores results in nuclear export and calpain-mediated degradation of β-catenin in the cytoplasm. Gαq does not inhibit the effects of constitutively activated ΔN-XTCF3-VP16 chimera in SW480 cells. Similarly, in HEK293 cells the Gq pathway suppresses β-catenin–T cell factor/lymphocyte enhancer factor-1 transcriptional activity induced by Wnt/Frizzled interaction or glycogen synthase kinase-3β-resistant β-catenin, but not ΔN-XTCF3-VP16. We conclude that Gq signaling promotes nuclear export and calpain-mediated degradation of β-catenin, which therefore contributes to the inhibition of Wnt/β-catenin pathway.