哈佛大学医学院Brigham and Women’s Hospital，哈佛医学院系统生物学系，哈佛癌症研究中心，Dana-Farber癌症研究所的研究人员在最新一期的Nature上发表研究进展GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer。
文章通讯作者是来自哈佛医学院的Lynda Chin教授，主要从事癌症分子遗传学与生物学方面的研究。
对多种固体癌分析发现，癌细胞的基因组上的5p13区域常发生拷贝数突变，包括，肺癌（56%），卵巢癌（38%），乳腺癌（32%），前列腺癌（37%）以及黑色素瘤（32%）。
Lynda Chin等人对基因组的该区域进行系统性分析发现：Golgi蛋白GOLPH3可能是癌症发生的一个关键因素。进一步体外和体内实验发现，GOLPH3是一个致癌基因。GOLPH3定位于Golgi网络上，并能与retromer（TOR信号通路上的靶位）相互作用。
遗传技术和生物学技术分析表明，GOLPH3是一个全新的致癌基因，能促进人类癌细胞增殖，同时还能调节癌细胞对rapamycin的敏感性。GOLPH3可能是癌症药物的有利靶位。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 459, 1085-1090 (25 June 2009) | doi:10.1038/nature08109
GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer
Kenneth L. Scott1,9, Omar Kabbarah1,9, Mei-Chih Liang1,4, Elena Ivanova2, Valsamo Anagnostou5, Joyce Wu1, Sabin Dhakal1, Min Wu1, Shujuan Chen1, Tamar Feinberg1, Joseph Huang1, Abdel Saci6, Hans R. Widlund3,7, David E. Fisher3,8, Yonghong Xiao2, David L. Rimm5, Alexei Protopopov2, Kwok-Kin Wong1,4 & Lynda Chin1,2,7
1 Department of Medical Oncology,
2 Belfer Institute for Applied Cancer Science,
3 Department of Pediatric Oncology, Dana-Farber Cancer Institute,
4 Ludwig Center at Dana-Farber/Harvard Cancer Center, Boston, Massachusetts 02115, USA
5 Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
6 Department of Systems Biology, Harvard Medical School,
7 Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
8 Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
9 These authors contributed equally to this work.
Genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma (32%). Here, using integrative analysis of a genomic profile of the region, we identify a Golgi protein, GOLPH3, as a candidate targeted for amplification. Gain- and loss-of-function studies in vitro and in vivo validated GOLPH3 as a potent oncogene. Physically, GOLPH3 localizes to the trans-Golgi network and interacts with components of the retromer complex, which in yeast has been linked to target of rapamycin (TOR) signalling. Mechanistically, GOLPH3 regulates cell size, enhances growth-factor-induced mTOR (also known as FRAP1) signalling in human cancer cells, and alters the response to an mTOR inhibitor in vivo. Thus, genomic and genetic, biological, functional and biochemical data in yeast and humans establishes GOLPH3 as a new oncogene that is commonly targeted for amplification in human cancer, and is capable of modulating the response to rapamycin, a cancer drug in clinical use.
