韓國科學(xué)家日前宣布,，他們發(fā)現(xiàn)了一種與肝癌病變有密切聯(lián)系的細(xì)胞膜受體。
首爾大學(xué)的研究小組說,，這個(gè)TM4SF5受體屬于細(xì)胞受體的四次跨膜蛋白家族,，在韓國77.8%的肝癌患者身上都可以找到。
該研究小組負(fù)責(zé)人說,，這一發(fā)現(xiàn)引人矚目,，因?yàn)樗状巫C實(shí)TM4SF5與肝癌患者之間有聯(lián)系。美國最新一期《臨床檢查雜志》（Journal of Clinical Investigation）月刊的網(wǎng)絡(luò)版刊登了這一研究結(jié)果。
研究人員早在1998年就發(fā)現(xiàn)TM4SF5與胰腺癌有關(guān)系,，但隨后沒人認(rèn)真去研究它是否會(huì)引發(fā)惡性腫瘤,。
科學(xué)家說，在證實(shí)TM4SF5引發(fā)肝癌之后,，可以推動(dòng)具體的研究,，以抑制有害的受體變得過度活躍。韓國其他研究人員已經(jīng)發(fā)現(xiàn)了一些物質(zhì)可以有效阻止細(xì)胞多層生長,。
這一最新發(fā)現(xiàn)是首爾大學(xué)研究小組與韓國光州科學(xué)技術(shù)院和慶北大學(xué)合作研究的結(jié)果,。（來源：新華網(wǎng)）
生物谷推薦原始出處：
（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.
