Bidirectional KCNQ1:β-catenin interaction drives colorectal cancer cell differentiation

Significance The K + channel KCNQ1 has been proposed as a tumor suppressor in colorectal cancer (CRC), but nothing is known about its regulatory role in early disease stages. KCNQ1 is a target gene of Wnt/β-catenin, which is tonically activated in CRC. We demonstrate a bidirectional interaction between KCNQ1 and β-catenin as a key regulator of CRC cell differentiation, proliferation, and invasion. KCNQ1 stabilizes β-catenin at adherent junctions to maintain an epithelial phenotype. The β-catenin:T-cell factor (TCF)-4 transcriptional pathway directly represses KCNQ1 expression, and the loss of KCNQ1 was associated with an epithelial–mesenchymal transition. The KCNQ1:KCNE3 ion channel complex expression in primary tumors was correlated with good survival outcome for patients with CRC. KCNQ1 is a potential early prognostic biomarker for CRC.

Kimelfe