PMID- 30548112 OWN - NLM STAT- MEDLINE DCOM- 20190211 LR - 20210109 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 110 IP - 2 DP - 2019 Feb TI - Sine oculis homeobox 1 promotes proliferation and migration of human colorectal cancer cells through activation of Wnt/beta-catenin signaling. PG - 608-616 LID - 10.1111/cas.13905 [doi] AB - Sine oculis homeobox 1 (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 are still poorly characterized. In the present study, we found that Six1 overexpression promoted the proliferation and migration of CRC cells. Consistently, Six1 knockdown (KD) significantly inhibited proliferation and migration of CRC cells. In addition, we showed that Six1 promoted proliferation and migration of CRC cells through activation of Wnt/beta-catenin signaling, as evidenced by promotion of nuclear localization of beta-catenin. Silencing of beta-catenin expression with siRNA or inhibiting Wnt signaling with a specific inhibitor, xav939, significantly blocked Six1-induced nuclear localization of beta-catenin and mitigated Six1-promoted proliferation and migration of CRC cells. We further confirmed the involvement of beta-catenin in Six1-promoted proliferation and migration of CRC cells by activation of Wnt signaling with lithium chloride (LiCl) in Six1 KD CRC cells and results showed that LiCl restores defective beta-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 the Wnt/beta-catenin signaling pathway, and strategies targeting Six1 may be promising for the treatment of CRC. CI - (c) 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Song, Wenxin AU - Song W AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. AD - Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, China. FAU - Ma, Jian AU - Ma J AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. FAU - Lei, Bingbing AU - Lei B AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. FAU - Yuan, Xin AU - Yuan X AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. FAU - Cheng, Binfeng AU - Cheng B AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. FAU - Yang, Haijie AU - Yang H AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. FAU - Wang, Mian AU - Wang M AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. FAU - Feng, Zhiwei AU - Feng Z AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. AD - Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, China. FAU - Wang, Lei AU - Wang L AUID- ORCID: 0000-0003-2678-2533 AD - School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, China. LA - eng GR - U1604166/National Natural Science Foundation of China/ GR - 81403161/National Natural Science Foundation of China/ GR - 201708410350/China Scholarship Council/ PT - Journal Article DEP - 20190128 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Homeodomain Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (SIX1 protein, human) RN - 0 (beta Catenin) SB - IM MH - Cell Line, Tumor MH - Cell Movement/*genetics MH - Cell Proliferation/*genetics MH - Colorectal Neoplasms/*genetics MH - Gene Expression Regulation, Neoplastic/genetics MH - HCT116 Cells MH - Homeodomain Proteins/*genetics MH - Humans MH - RNA, Small Interfering/genetics MH - Signal Transduction/genetics MH - Wnt Signaling Pathway/*genetics MH - beta Catenin/*genetics PMC - PMC6361609 OTO - NOTNLM OT - Six1 OT - colorectal cancer OT - migration OT - proliferation OT - beta-catenin EDAT- 2018/12/15 06:00 MHDA- 2019/02/12 06:00 PMCR- 2019/02/01 CRDT- 2018/12/15 06:00 PHST- 2018/07/30 00:00 [received] PHST- 2018/11/29 00:00 [revised] PHST- 2018/12/02 00:00 [accepted] PHST- 2018/12/15 06:00 [pubmed] PHST- 2019/02/12 06:00 [medline] PHST- 2018/12/15 06:00 [entrez] PHST- 2019/02/01 00:00 [pmc-release] AID - CAS13905 [pii] AID - 10.1111/cas.13905 [doi] PST - ppublish SO - Cancer Sci. 2019 Feb;110(2):608-616. doi: 10.1111/cas.13905. Epub 2019 Jan 28.