title: DLX4 upregulates TWIST and enhances tumor migration, invasion and metastasis.
abstract: 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.
authors.affiliation: Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Luzhou Medical College, Luzhou 646000, China.
authors.forename: Lianmei
authors.initials: L
authors.lastname: Zhang
authors.forename: Manman
authors.initials: M
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Gan
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.forename: Xiuli
authors.initials: X
authors.lastname: Xiao
authors.forename: M David
authors.initials: MD
authors.lastname: Stewart
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Luquan
authors.initials: L
authors.lastname: Yang
authors.forename: Tiandan
authors.initials: T
authors.lastname: Zhang
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Junjiang
authors.initials: J
authors.lastname: Fu
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*
chemical_list: C105304:DLX4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D008156:Luciferases
keywords: DLX4; E-Cadherin; TWIST; breast cancer; metastasis