Research Paper Volume 12, Issue 9 pp 8372—8396
KIF23 activated Wnt/β-catenin signaling pathway through direct interaction with Amer1 in gastric cancer
- 1 Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
- 2 Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
received: November 5, 2019 ; accepted: March 9, 2020 ; published: May 4, 2020 ;https://doi.org/10.18632/aging.103146
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Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Increased expression of the kinesin family member 23 (KIF23) has been verified in gastric cancer (GC) and its upregulation contributes to cell proliferation. Even though, the role of KIF23 has not been fully elucidated in GC, and the mechanisms of KIF23 as an oncogene remain unknown. To further identify its potential role in GC, we analyzed gene expression data from GC patients in GEO and TCGA datasets. KIF23 was upregulated in GC, and increased expression of KIF23 correlated with poor prognosis. Importantly, KIF23 inhibition not only suppressed GC cell proliferation, tumorigenesis, but also migration and invasion, and arrested the cell cycle in the G2/M phase. Mechanistic investigations confirmed that KIF23 activated the Wnt/β-catenin signaling pathway by directly interacting with APC membrane recruitment 1 (Amer1). Furthermore, KIF23 exhibited competitive binding with Amer1 to block the association of Amer1 with adenomatous polyposis coli (APC), thus relocating Amer1 from the membrane and cytoplasm to the nucleus and attenuating the ability of Amer1 to negatively regulate Wnt/β-catenin signaling, resulting in activation of this signaling pathway. Collectively, our findings demonstrated that KIF23 promoted GC cell proliferation by directly interacting with Amer1 and activating the Wnt/β-catenin signaling pathway.
GC: gastric cancer; KIF23: kinesin family member 23; MKLP1: mitotic kinesin like protein; Amer1: APC membrane recruitment 1; APC: adenomatous polyposis coli; TCGA: The Cancer Genome Atlas; GSAE: gene set enrichment analysis; GEO: Gene Expression Omnibus; IHC: immunohistochemistry; PRC1: microtubule-associated protein1; IF: Immunofluorescence; Co-IP: coimmunoprecipitation.