Six1 promotes proliferation and migration of human colorectal cancer cells through activating Wnt/β-catenin signaling.

Six1 promotes proliferation and migration of human colorectal cancer cells through activating Wnt/β-catenin signaling.

Cancer Sci. 2018 Dec 10;:

Authors: Song W, Ma J, Lei B, Yuan X, Cheng B, Yang H, Wang M, Feng Z, Wang L

Abstract
Six1 is a homeodomain transcription factor that is aberrantly expressed in a variety of human cancers, including colorectal cancer (CRC). Six1 has been reported to play a key role in the proliferation and migration of CRC cells but the underlying molecular mechanisms is still poorly characterized. In the present study, we found that Six1 overexpression promoted the proliferation and migration of CRC cells. Consistently, Six1 knock-down (KD) significantly inhibited proliferation and migration of CRC cells. In addition, we showed that Six1 promoted proliferation and migration of CRC cells through activating Wnt/β-catenin signaling, as evidenced by promoting nuclear localization of β-catenin. Silencing of β-catenin expression with siRNA or inhibiting Wnt signaling with a specific inhibitor, xav939, significantly blocked Six1-induced nuclear localization of β-catenin and mitigated Six1-promoted proliferation and migration of CRC cells. We further confirmed the involvement of β-catenin in Six1-promoted proliferation and migration of CRC cells by activation Wnt signaling with lithium chloride (LiCl) in Six1 KD CRC cells and results showed that LiCl restores the defective β-catenin nuclear localization and proliferation and migration of CRC cells. Taken together, these results suggest that Six1 homeoprotein promotes the proliferation and migration of CRC cells by activating Wnt/β-catenin signaling pathway and strategies targeting Six1 may be promising for the treatment of CRC. This article is protected by copyright. All rights reserved.

PMID: 30548112 [PubMed - as supplied by publisher]

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