3月17日，美国科学家说，通过阻断一种名为Skp2的基因，能够使癌细胞老化并死亡。这一发现或许能为治疗癌症提供一种新方法。
美国哈佛大学医学院基因学家皮耶尔·保罗·潘多尔菲介绍，阻断癌细胞中的Skp2基因能够触发“衰老进程”，迫使癌细胞像体细胞暴露在阳光下那样“干死”，无法无限分裂、在人体内转移。
“我们发现，如果你(以阻断基因方式)破坏细胞，细胞就会生成一种内在机制，使它们生病，”潘多尔菲说，“这种机制以不可逆转方式阻止它们生长。”
潘多尔菲等研究人员以两组老鼠为对象进行实验。这些老鼠在基因经过改造后会患上一种前列腺癌，但其中一组老鼠的Skp2基因遭阻断。6个月后，这组老鼠没有长出肿瘤，而Skp2基因未遭阻断的另一组老鼠长出肿瘤。
他们从那组没有长肿瘤的老鼠身上提取淋巴腺和前列腺组织，发现其中许多癌细胞开始老化，细胞分裂速度变慢。
研究人员向实验鼠体内植入人类癌细胞，结果也发现这些癌细胞发生老化。
潘多尔菲说，这种相关Skp2基因的老化进程看起来仅对癌细胞起作用，对其他细胞没有影响，“我们可没打算让癌症患者衰老”。
这一发现成果发表于最新一期《自然》Nature期刊上。(生物谷Bioon.com)
Science：首次发现细胞凋亡开关 有助癌症治疗
PLoS One：美国癌症死亡率显著下降
Cell：肥胖者易得癌症
生物谷推荐原文出处：
Nature doi:10.1038/nature08815
Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence
Hui-Kuan Lin1,2,3, Zhenbang Chen1,2,4,6, Guocan Wang1,2,4,7, Caterina Nardella1,2,4,7, Szu-Wei Lee3,7, Chan-Hsin Chan3, Wei-Lei Yang3, Jing Wang3, Ainara Egia4, Keiichi I. Nakayama5, Carlos Cordon-Cardo2,6, Julie Teruya-Feldstein2 & Pier Paolo Pandolfi1,2,4
Cancer Biology and Genetics Program,
Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
Cancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan
Present addresses: Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 Dr D. B. Todd Jr Boulevard, Nashville, Tennessee 37208-3599, USA (Z.C.); Irving Cancer Research Center, Room 309, 1130 St. Nicholas Avenue, New York, New York 10032, USA (C.C.-C.).
Cellular senescence has been recently shown to have an important role in opposing tumour initiation and promotion. Senescence induced by oncogenes or by loss of tumour suppressor genes is thought to critically depend on induction of the p19Arf–p53 pathway. The Skp2 E3-ubiquitin ligase can act as a proto-oncogene and its aberrant overexpression is frequently observed in human cancers. Here we show that although Skp2 inactivation on its own does not induce cellular senescence, aberrant proto-oncogenic signals as well as inactivation of tumour suppressor genes do trigger a potent, tumour-suppressive senescence response in mice and cells devoid of Skp2. Notably, Skp2 inactivation and oncogenic-stress-driven senescence neither elicit activation of the p19Arf–p53 pathway nor DNA damage, but instead depend on Atf4, p27 and p21. We further demonstrate that genetic Skp2 inactivation evokes cellular senescence even in oncogenic conditions in which the p19Arf–p53 response is impaired, whereas a Skp2–SCF complex inhibitor can trigger cellular senescence in p53/Pten-deficient cells and tumour regression in preclinical studies. Our findings therefore provide proof-of-principle evidence that pharmacological inhibition of Skp2 may represent a general approach for cancer prevention and therapy.
