HIF-1alpha hinders mismatch repair

The infamous hypoxia-induced factor enhances risk of genetic instability, study shows

Clementine Wallace(clementine.wallace@gmail.com)
Mar 20, 2005

A newly found mechanism that promotes the appearance of mutations under hypoxic conditions is reported in the March 18 issue of Molecular Cell. In the oxygen-deprived microenvironment of certain tumors, the genetic instabilities that ensue stimulate tumor progression and metastasis.

Eric Huang, from the National Cancer Institute in Bethesda, Md., and colleagues were studying HIF-1α, the hypoxia-induced transcription factor, which is known to upregulate a variety of hypoxia-related genes. HIF-1α is often overexpressed in tumors because different factors induce its expression.

Huang's team found that, under certain cellular conditions, HIF-1α is also responsible for hindering the cell's mismatch repair (MMR) system, crucial for maintaining a cell's genetic integrity. "Cancer cells already divide more frequently than others, so they develop more mutations," said Franklin Bunn, from Harvard Medical School, Cambridge, Massachusetts, who did not participate in the study. "Impairing the MMR system further enhances the...

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