Int J Biol Sci 2012; 8(8):1178-1187. doi:10.7150/ijbs.4458
DLX4 Upregulates TWIST and Enhances Tumor Migration, Invasion and Metastasis
1. Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Luzhou Medical College, Luzhou, China 646000
The distal-less homeobox gene 4 (DLX4) is a member of the DLX family of homeobox genes. Although absent from most normal adult tissues, DLX4 is widely expressed in leukemia, lung, breast, ovarian and prostate cancers. However the molecular targets, mechanisms and pathways that mediate the role of DLX4 in tumor metastasis are poorly understood. In this study, we found that DLX4 induces cancer cells to undergo epithelial to mesenchymal transition (EMT) through TWIST. Overexpression of DLX4 increased expression of TWIST expression in cancer cell lines, resulting in increased migratory and invasive capacity. Likewise, knocking down expression of DLX4 decreased TWIST expression and the migration ability of cancer cell lines. DLX4 bound to regulatory regions of the TWIST gene. Both western blotting and immunohistochemistry staining showed that the expression of DLX4 and TWIST are correlated in most of breast tumors. Taken together, these data from both cell models and tumor tissues demonstrate that DLX4 not only upregulates TWIST expression but also induces EMT and tumor metastasis. Altogether, we propose a new pathway in which DLX4 drives expression of TWIST to promote EMT, cancer migration, invasion and metastasis.
Keywords: DLX4, TWIST, E-Cadherin, breast cancer, metastasis
This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Zhang L, Yang M, Gan L, He T, Xiao X, Stewart MD, Liu X, Yang L, Zhang T, Zhao Y, Fu J. DLX4 Upregulates TWIST and Enhances Tumor Migration, Invasion and Metastasis. Int J Biol Sci 2012; 8(8):1178-1187. doi:10.7150/ijbs.4458. Available from http://www.ijbs.com/v08p1178.htm