韩国科学家日前宣布,他们发现了一种与肝癌病变有密切联系的细胞膜受体。
首尔大学的研究小组说,这个TM4SF5受体属于细胞受体的四次跨膜蛋白家族,在韩国77.8%的肝癌患者身上都可以找到。
该研究小组负责人说,这一发现引人瞩目,因为它首次证实TM4SF5与肝癌患者之间有联系。美国最新一期《临床检查杂志》(Journal of Clinical Investigation)月刊的网络版刊登了这一研究结果。
研究人员早在1998年就发现TM4SF5与胰腺癌有关系,但随后没人认真去研究它是否会引发恶性肿瘤。
科学家说,在证实TM4SF5引发肝癌之后,可以推动具体的研究,以抑制有害的受体变得过度活跃。韩国其他研究人员已经发现了一些物质可以有效阻止细胞多层生长。
这一最新发现是首尔大学研究小组与韩国光州科学技术院和庆北大学合作研究的结果。(来源:新华网)
生物谷推荐原始出处:
(Journal of Clinical Investigation),doi:10.1172/JCI33768,Sin-Ae Lee,Jung Weon Lee
Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma
Sin-Ae Lee1,2, Sung-Yul Lee1,2, Ik-Hyun Cho3, Min-A Oh1,4, Eun-Sil Kang1,2, Yong-Bae Kim1,4, Woo Duck Seo5, Suyong Choi1,4, Ju-Ock Nam6, Mimi Tamamori-Adachi7, Shigetaka Kitajima7, Sang-Kyu Ye8, Semi Kim9, Yoon-Jin Hwang10, In-San Kim6, Ki Hun Park5 and Jung Weon Lee1,2,4
1Cancer Research Institute, College of Medicine, and Cell Dynamics Research Center,
2Department of Molecular and Clinical Oncology,
3College of Dentistry and Dental Research Institute, and
4Department of Tumor Biology, Seoul National University, Seoul, Republic of Korea.
5Division of Applied Life Science, Gyeongsang National University, Jinju, Republic of Korea.
6Department of Biochemistry, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
7Department of Biochemical Genetics, Tokyo Medical and Dental University, Tokyo, Japan.
8Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
9Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
10Department of Surgery, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Abstract
The growth of normal cells is arrested when they come in contact with each other, a process known as contact inhibition. Contact inhibition is lost during tumorigenesis, resulting in uncontrolled cell growth. Here, we investigated the role of the tetraspanin transmembrane 4 superfamily member 5 (TM4SF5) in contact inhibition and tumorigenesis. We found that TM4SF5 was overexpressed in human hepatocarcinoma tissue. TM4SF5 expression in clinical samples and in human hepatocellular carcinoma cell lines correlated with enhanced p27Kip1 expression and cytosolic stabilization as well as morphological elongation mediated by RhoA inactivation. These TM4SF5-mediated effects resulted in epithelial-mesenchymal transition (EMT) via loss of E-cadherin expression. The consequence of this was aberrant cell growth, as assessed by S-phase transition in confluent conditions, anchorage-independent growth, and tumor formation in nude mice. The TM4SF5-mediated effects were abolished by suppressing the expression of either TM4SF5 or cytosolic p27Kip1, as well as by reconstituting the expression of E-cadherin. Our observations have revealed a role for TM4SF5 in causing uncontrolled growth of human hepatocarcinoma cells through EMT.