Grainyhead-like 2 as a double-edged sword in development and cancer

• Type of Material: Article
• Authors: Jiaxing He, Second Hospital of Jilin University; Chunyang Feng, Second Hospital of Jilin University; He Zhu, Second Hospital of Jilin University; Shuying Wu, Second Hospital of Jilin University; Peng Jin, Emory University; Tianmin Xu, Second Hospital of Jilin University
• Language: English
• Date: 2020-01-01
• Publisher: E-CENTURY PUBLISHING CORP
• Publication Version: Final Published Version
• Copyright Statement: © 2020 E-Century Publishing Corporation. All rights reserved.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Title of Journal or Parent Work: AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
• Volume: 12
• Issue: 2
• Start Page: 310
• End Page: 331
• Grant/Funding Information: This work was funded by grants from the Department of Science and Technology of Jilin Province (20190101014JH), Department of Science and Technology of Jilin Province (20180203032YY) and National Key R&D Program of China (2016YFC1302901).
• Keywords: Grainyhead-like 2; neural tube closure; EPITHELIAL-MESENCHYMAL TRANSITION; epithelial morphogenesis; ESTROGEN-RECEPTOR-ALPHA; Science & Technology; FEEDBACK LOOP; Life Sciences & Biomedicine; GENE GRHL2; tumorigenesis; TUMOR SUPPRESSION; estrogen receptor; epithelial-to-mesenchymal; HEARING-LOSS; Medicine, Research & Experimental; Oncology; TRANSCRIPTION FACTOR FAMILY; HUMAN TELOMERASE; Research & Experimental Medicine; EXPRESSION PATTERNS; NEURAL-TUBE CLOSURE
• Research Categories: Biology, Cell; Biology, Genetics; Health Sciences, Oncology

Abstract

Grainyhead-like 2 (GRHL2), one of the three homologs of Drosophila grainyhead, contributes to epithelial morphogenesis and differentiation. Dysregulation of GRHL2 has been shown to be involved in hearing loss and neural tube defects during embryogenesis. Moreover, it is well-recognized that GRHL2 suppresses epithelial-to-mesenchymal transition (EMT) that is required for migration and invasion of carcinoma, implicating, GRHL2 in carcinogenesis. Diverse mechanisms, as well as the varied roles of GRHL2 in different tumor tissues, have been elucidated. However, the functions of GRHL2 appear to be more complicated than initially thought. GRHL2, acting as either a tumor enhancer or a tumor inhibitor, depends on the type of cancer. In this review, we summarize research progress about normal physiological functions of GRHL2 including epithelial morphogenesis, neural tube closure, and hearing loss. Moreover, the mechanisms of GRHL2 in tumorigenesis, containing EMT suppression, forming a negative feedback loop with ZEB1 and miR200 family, interactions with estrogen receptor (ER)-dependent signaling pathway, regulation of telomerase reverse transcriptase and relationships with TGF-beta signaling pathway are discussed in this review in an effort to better understand the roles of GRHL2 in a variety of cancers toward the goal of GRHL2-targeted treatment in the near future.