| 摘要: |
| 粒状头样2(GRHL2)作为果蝇GRH(grainyhead)基因在哺乳动物中的同源基因之一,不仅参与调控胚胎发育、表皮屏障形成、表皮损伤修复以及中枢神经系统的发育等诸多生命活动过程,而且在乳腺癌、肝癌、口腔鳞状细胞癌等多种肿瘤的发生发展中发挥着重要作用。GRHL2在肝癌、乳腺癌、口腔鳞状细胞癌等肿瘤中表达升高,促进肿瘤细胞增殖,抑制细胞凋亡;而在上皮-间质转化(EMT)相关的乳腺癌中则下调表达,促进EMT的发生。GRHL2在肿瘤细胞中作用机制复杂而多样,既包括死亡受体相关的凋亡作用,人端粒反转录酶(hTERT)的活化,也涉及到EMT的发生、失巢凋亡敏感性增加。随着对GRHL2研究的深入,将有望为恶性肿瘤的临床诊断和治疗开辟新的方向。 |
| 关键词: 粒状头样2 肿瘤 上皮-间质转化 |
| DOI： |
| 投稿时间：2013-03-05修订日期：2013-06-17 |
| 基金项目:国家自然科学基金(81272780). |
|
| Grainyhead-like-2 (GRHL2) and carcinogenesis: an advance |
| TANG Guan nan,YAN Hong li,WANG Yu zhao,SUN Shu han* |
(Department of Medical Genetics, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China
*Corresponding author.) |
| Abstract: |
| Grainyhead-like-2 (GRHL2), a mammalian homolog of Drosophila grainyhead (GRH), is involved in a variety of biological processes, including mammalian embryonic development, epidermal barrier maturation, epithelial wound healing, and central nervous system development. Notably, GRHL2 is also essential for tumor origination and development in various kinds of cancer tissues, such as hepatocellular carcinoma, breast cancer and oral squamous cell carcinoma. In these cancer cells, GRHL2 expression is markedly enhanced, and the gain of GRHL2 can significantly facilitate cancer cell proliferation and inhibit apoptosis. On contrast, in epithelial-mesenchymal transition (EMT) related breast cancer, the down-regulated GRHL2 can promote the EMT process. The underlying mechanisms of GRHL2 in tumorigenesis remain complex and diverse, including the death receptor-mediated apoptosis, aberrant activation of the human telomerase reverse transcriptase(hTERT), EMT, and enhanced anoikis-sensitivity as well. We believe that further research on GRHL2 may cast new lights on cancer therapy. |
| Key words: grainyhead-like-2 neoplasms epithelial-mesenchymal transition |
