Taiwan researchers discover protein that boosts cancer cell growth

2011/08/24  Taipei, Aug. 24 (CNA) An Academia Sinica research team has identified a protein -- called KLHL 20 -- that plays a key role in tumor progression, a discovery that could provide a new focus for future research into treating aggressive tumors. In a statement released by Taiwan's top academic institution on Wednesday, research team leader Chen Ruey-hwa said the KLHL 20 protein was induced by a protein called HIF-1, a key target of cancer researchers. HIF-1 regulates a large panel of genes that promote tumor cell survival in low oxygen conditions, induce cancer cell migration and contribute to resistance to chemotherapy and radiotherapy. Understanding how tumor cells control HIF-1 synthesis has long been an attractive cancer research topic and considered to be a major target for pharmaceutical intervention in cancer therapy, said Chen, deputy director of Academia Sinica's Institute of Biological Chemistry. The link to HIF-1 is key, Chen said, because of KLHL 20's ability to form a complex with proteins Cullin 3 and Roc 1 that can cause degradation of the protein PML, a well-known tumor suppressor protein. "PML itself inhibits HIF-1. Thus, the HIF-1-induced PML degradation successfully relieves the inhibitory effect of PML on HIF-1," Chen explained. Tumor cells, Chen added, exploit this mechanism to amplify HiF-1 production in the early phase of hypoxia or low oxygen conditions, thereby aiding tumor progression. The identification of KLHL 20's role in the mechanism could offer a new target for cancer drugs to break down HIF-1's proliferation and resistance to proteins or treatments, the Academia Sinica statement said. The study done by Chen's team has been published in the latest issue of leading cancer journal "Cancer Cell." The full article, called "A cullin3-KLHL20 ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression" can be found online at the Cancer Cell website at: http://www.sciencedirect.com/science/article/pii/S1535610811002637. (By Hsu Chih-wei and Sofia Wu) enditem/ls