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Int J Biol Sci 2018; 14(9):1067-1080. doi:10.7150/ijbs.23845

Research Paper

WDR1 Promotes Cell Growth and Migration and Contributes to Malignant Phenotypes of Non-small Cell Lung Cancer through ADF/cofilin-mediated Actin Dynamics

Baiyin Yuan1,*,✉, Ruirui Zhang1,*, Jisheng Hu1, Zhongying Liu1, Chao Yang1, Tongcun Zhang1,✉, Chenxi Zhang2,✉

1. Biomedical Research Institute, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei Province 430081, China.
2. Central Laboratory, Nanjing Chest Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province 210029, P.R. China.
* These authors contributed equally to this work.

Abstract

The characteristic of carcinoma is cell migration and invasion, which involve in strong actin dynamics. Regulations of actin dynamics have been implicated in cancer cell migration and tumor progression. WDR1 (WD-repeat domain 1) is a major cofactor of the actin depolymerizing factor (ADF)/cofilin, strongly accelerating ADF/cofilin-mediated actin disassembly. The role of WDR1 in non-small cell lung cancer (NSCLC) progression has been unknown. Here, we show that the expression levels of WDR1 are increased in human NSCLC tissues compared with adjacent non-tumor tissues, and high WDR1 level correlates with poor prognosis in NSCLC patients. Knockdown of WDR1 in NSCLC cells significantly inhibits cell migration, invasion, EMT process and tumor cell growth in vitro and in vivo. Otherwise, overexpression of WDR1 promotes NSCLC cell proliferation and migration. Mechanically, our data suggested WDR1 regulated tumor cells proliferation and migration might through actin cytoskeleton-mediated regulation of YAP, and we demonstrated that WDR1 contributes to NSCLC progression through ADF/cofilin-mediated actin disassembly. Our findings implicate that the ADF/cofilin-WDR1-actin axis as an activator of malignant phenotype that will be a promising therapeutic target in lung cancer.

Keywords: WDR1, Cancer, Non-small cell lung cancer, Actin dynamics, ADF/cofilin

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Yuan B, Zhang R, Hu J, Liu Z, Yang C, Zhang T, Zhang C. WDR1 Promotes Cell Growth and Migration and Contributes to Malignant Phenotypes of Non-small Cell Lung Cancer through ADF/cofilin-mediated Actin Dynamics. Int J Biol Sci 2018; 14(9):1067-1080. doi:10.7150/ijbs.23845. Available from http://www.ijbs.com/v14p1067.htm