哈佛大學醫(yī)學院Brigham and Women’s Hospital,，哈佛醫(yī)學院系統(tǒng)生物學系，哈佛癌癥研究中心,，Dana-Farber癌癥研究所的研究人員在最新一期的Nature上發(fā)表研究進展GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer,。
文章通訊作者是來自哈佛醫(yī)學院的Lynda Chin教授，主要從事癌癥分子遺傳學與生物學方面的研究,。
對多種固體癌分析發(fā)現(xiàn),，癌細胞的基因組上的5p13區(qū)域常發(fā)生拷貝數(shù)突變，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等人對基因組的該區(qū)域進行系統(tǒng)性分析發(fā)現(xiàn)：Golgi蛋白GOLPH3可能是癌癥發(fā)生的一個關(guān)鍵因素。進一步體外和體內(nèi)實驗發(fā)現(xiàn),，GOLPH3是一個致癌基因,。GOLPH3定位于Golgi網(wǎng)絡(luò)上,，并能與retromer（TOR信號通路上的靶位）相互作用。
遺傳技術(shù)和生物學技術(shù)分析表明,，GOLPH3是一個全新的致癌基因,，能促進人類癌細胞增殖，同時還能調(diào)節(jié)癌細胞對rapamycin的敏感性,。GOLPH3可能是癌癥藥物的有利靶位,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
