来自台湾中央研究院的杨泮池院士领衔的研究团队发现了p53的抑癌新机制。P53一直是为人熟知的抑癌基因，人类50%的癌症与该基因有关，包括，肝癌、肺癌、胃癌、食道癌、结肠癌、卵巢癌等等。然而，目前关于p53与癌症的研究只是p53机制的冰山一角，人类离获得p53的全景还有一定的距离。
杨泮池领衔的研究团队由台湾大学医学院，国防医学院、及成大学医学院，中央研究院的科研人员组成。他们的研究发现，在正常的细胞中，p53及其下游分子MDM2可以调控促癌转移分子Slug，透过形成p53-MDM2-Slug复合体改变Slug的稳定性，因而抑制癌细胞转移能力。然而，一旦p53发生变异，突变的p53即丧失控制Slug蛋白稳定性的能力，细胞内不断累积的Slug蛋白促使癌细胞获得强大的转移能力，最终导致癌细胞扩散至全身。
杨泮池院士指出，除了细胞生物学的基础研究之外，p53-MDM2-Slug调控路径同时也在临床肺癌检测中获得验证，肺癌的扩散路径正是p53-MDM2-Slug通路。
研究小组还应用siRNA阻断变异的p53-MDM2-Slug路径，用以防止癌症扩散。同时，还与旅美中央院院士李国雄合作，利用他研发的专利化合物进行细胞试验，研究结果证实低剂量的该化合物就能阻断Slug路径。(生物谷Bioon.com)
生物谷推荐原始出处：
Nature Cell Biology 17 May 2009 doi:10.1038/ncb1875
p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug
Shu-Ping Wang1, Wen-Lung Wang1, Yih-Leong Chang2, Chen-Tu Wu2, Yu-Chih Chao1, Shih-Han Kao3, Ang Yuan4, Chung-Wu Lin5, Shuenn-Chen Yang6, Wing-Kai Chan7, Ker-Chau Li8, Tse-Ming Hong9,11 & Pan-Chyr Yang4,6,10,11
The tumour suppressor p53 is known to prevent cancer progression by inhibiting proliferation and inducing apoptosis of tumour cells. Slug, an invasion promoter, exerts its effects by repressing E-cadherin transcription. Here we show that wild-type p53 (wtp53) suppresses cancer invasion by inducing Slug degradation, whereas mutant p53 may stabilize Slug protein. In non-small-cell lung cancer (NSCLC), mutation of p53 correlates with low MDM2, high Slug and low E-cadherin expression. This expression profile is associated with poor overall survival and short metastasis-free survival in patients with NSCLC. wtp53 upregulates MDM2 and forms a wtp53–MDM2–Slug complex that facilitates MDM2-mediated Slug degradation. Downregulation of Slug by wtp53 or MDM2 enhances E-cadherin expression and represses cancer cell invasiveness. In contrast, mutant p53 inactivates Slug degradation and leads to Slug accumulation and increased cancer cell invasiveness. Our findings indicate that wtp53 and p53 mutants may differentially control cancer invasion and metastasis through the p53–MDM2–Slug pathway.
1 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
2 Department of Pathology and Graduate Institute of Pathology, National Taiwan University, Taipei 10043, Taiwan.
3 Graduate Institute of Molecular Biology, College of Medicine, National Taiwan University, Taipei 10043, Taiwan.
4 Department of Internal Medicine, National Taiwan University Hospital, Taipei 10043, Taiwan.
5 Department of Pathology, National Taiwan University Hospital, Taipei 10043, Taiwan.
6 Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
7 Department of Medical Research, National Taiwan University Hospital, Taipei 10043, Taiwan.
8 Institute of Statistical Science, Academia Sinica, Taipei, 11529, Taiwan.
9 Institute of Clinical Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
10 NTU Center for Genomic Medicine, College of Medicine, National Taiwan University, Taipei 10043, Taiwan.
11 These authors contributed equally to this work.
