title: Grhl3 induces human epithelial tumor cell migration and invasion via downregulation of E-cadherin.
abstract: Grainyhead genes are involved in wound healing and developmental neural tube closure. Metastasis is a multistep process during which cancer cells disseminate from the site of primary tumors and establish secondary tumors in distant organs. The adhesion protein E-cadherin plays an essential role in metastasis. In light of the high degree of similarity between the epithelial-mesenchymal transition (EMT) occurring in wound-healing processes and the EMT occurring during the acquisition of invasiveness in skin or breast cancer, we investigated the role of the Grainyhead genes in cancer invasion. Here, we show that there is an inverse relationship between Grainyhead-like 3 (Grhl3) and E-cadherin expression in some epithelial tumor cell lines. Overexpression of Grhl3 in the E-cadherin-positive epithelial tumor cell line, characterized by less invasiveness, generated a transcriptional blockage of the E-cadherin gene and promoted cell migration and cell invasion. Conversely, Grhl3 depletion inhibited cell migration and cell invasion and was associated with a gain of E-cadherin expression. To further explore the mechanism by which Grhl3 regulated E-cadherin expression, an E-cadherin promoter report analysis was performed and results showed that Grhl3 repressed E-cadherin gene expression by directly or indirectly binding to the E-boxes present in the proximal E-cadherin promoter. Taken together, our findings define a major role for Grhl3 in the induction of migration and invasion by the downregulation of E-cadherin in cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei 230032, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei 230032, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei 230032, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Di
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei 230032, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zha
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei 230032, China Institute of Dermatology, Anhui Medical University, Hefei 230032, China haishengs@ahmu.edu.cn.
authors.forename: Haisheng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Institute of Dermatology, Anhui Medical University, Hefei 230032, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D015820:Cadherins / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; C473143:GRHL3 protein, human; D014157:Transcription Factors
keywords: E-cadherin; Grhl3; breast cancer; invasion; migration; skin cancer
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