A study by an Academia Sinica research team has identified a protein — called KLHL 20 — that plays a key role in the progression of tumors, a discovery that could provide a new focus for future research into treating aggressive tumors.
In a statement released by the nation’s top academic institution yesterday, research team leader Chen Ruey-hwa (陳瑞華) said the KLHL 20 protein was induced by a protein called HIF-1, a key target of cancer researchers.
HIF-1 regulates a large number of genes that promote tumor cell survival in low-oxygen conditions, induce cancer cell migration and contribute to chemotherapy and radiotherapy resistance.
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 degrade the protein PML, a well-known tumor suppressing protein.
“PML itself inhibits HIF-1. Thus, the HIF-1-induced PML degradation successfully relieves the inhibitory effect of PML on HIF-1,” Chen said.
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 and treatments, the statement said.
The study was published in the latest issue of the leading cancer journal, Cancer Cell. The full article can be found online at the Cancer Cell Web site.