据外媒7月13日报道，英国研究人员首次发现，有两个基因在人体自身细胞抗击癌症细胞的过程中发挥着重要作用。发表在7月13日《公共科学图书馆生物学》（PLoS Biology）期刊网络版上的此项发现，将可能导致出现全新的癌症研究概念，那就是未来的癌症疗法将通过使人体自身的健康细胞“装备更为精良”来攻击癌细胞。
由英国伦敦大学学院分子细胞生物学和细胞生物学部开展的此项研究证明，正常细胞与癌细胞在人体中上演着一场“你死我活”的较量。如果非癌变细胞获得了优势，会将癌细胞团团围住，癌细胞就会死亡；如果癌细胞设法挣脱了束缚，它们将继续不受干扰地进行分裂和生长。这项研究表明，Lgl蛋白和Mahjong蛋白在细胞的这场较量中发挥了关键作用，影响着这些细胞究竟会“鹿死谁手”。这种细胞竞争形式先前曾被证明在果蝇中出现过，不过在哺乳动物身上发现尚属首次。
该项研究的主持者、伦敦大学学院的藤田泰之博士表示，这是首次发现癌症细胞只需被健康细胞包围即可被杀死。以此为基础，科学家们将能加深对癌症机制的理解，进而发现预防和治疗癌症的全新方式。
20年后全球每年死于癌症的人数将翻番
推荐原文出处：
PLoS Biology doi:10.1371/journal.pbio.1000422
Involvement of Lgl and Mahjong/VprBP in Cell Competition
Yoichiro Tamori1, Carl Uli Bialucha2¤a, Ai-Guo Tian1¤b, Mihoko Kajita2, Yi-Chun Huang1, Mark Norman2, Nicholas Harrison1, John Poulton1¤c, Kenzo Ivanovitch2, Lena Disch2, Tao Liu2, Wu-Min Deng1#*, Yasuyuki Fujita2,3,4#*
1 Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America, 2 MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London, United Kingdom, 3 Department of Cell and Developmental Biology, University College London, London, United Kingdom, 4 Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan
During the initial stages of carcinogenesis, transformation events occur in a single cell within an epithelial monolayer. However, it remains unknown what happens at the interface between normal and transformed epithelial cells during this process. In Drosophila, it has been recently shown that normal and transformed cells compete with each other for survival in an epithelial tissue; however the molecular mechanisms whereby “loser cells” undergo apoptosis are not clearly understood. Lgl (lethal giant larvae) is a tumor suppressor protein and plays a crucial role in oncogenesis in flies and mammals. Here we have examined the involvement of Lgl in cell competition and shown that a novel Lgl-binding protein is involved in Lgl-mediated cell competition. Using biochemical immunoprecipitation methods, we first identified Mahjong as a novel binding partner of Lgl in both flies and mammals. In Drosophila, Mahjong is an essential gene, but zygotic mahjong mutants (mahj?/?) do not have obvious patterning defects during embryonic or larval development. However, mahj?/? cells undergo apoptosis when surrounded by wild-type cells in the wing disc epithelium. Importantly, comparable phenomena also occur in Mahjong-knockdown mammalian cells; Mahjong-knockdown Madin-Darby canine kidney epithelial cells undergo apoptosis, only when surrounded by non-transformed cells. Similarly, apoptosis of lgl?/? cells is induced when they are surrounded by wild-type cells in Drosophila wing discs. Phosphorylation of the c-Jun N-terminal kinase (JNK) is increased in mahj?/? or lgl?/? mutant cells, and expression of Puckered (Puc), an inhibitor of the JNK pathway, suppresses apoptosis of these mutant cells surrounded by wild-type cells, suggesting that the JNK pathway is involved in mahj- or lgl-mediated cell competition. Finally, we have shown that overexpression of Mahj in lgl?/? cells strongly suppresses JNK activation and blocks apoptosis of lgl?/? cells in the wild-type wing disc epithelium. These data indicate that Mahjong interacts with Lgl biochemically and genetically and that Mahjong and Lgl function in the same pathway to regulate cellular competitiveness. As far as we are aware, this is the first report that cell competition can occur in a mammalian cell culture system.
