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Heat-shock factor reveals its unique role in supporting highly malignant cancers
Date:8/2/2012

CAMBRIDGE, Mass. (August 2, 2012) Whitehead Institute researchers have found that increased expression of a specific set of genes is strongly associated with metastasis and death in patients with breast, colon, and lung cancers. Not only could this finding help scientists identify a gene profile predictive of patient outcomes and response to treatment, it could also guide the development of therapeutics to target multiple cancer types.

The genes identified are activated by a transcription factor called heat-shock factor 1 (HSF1) as part of a transcriptional program distinct from HSF1's well-known role in mediating the response of normal cells to elevated temperature.

In normal cells, a variety of stressors, including heat, hypoxia, and toxins, activate HSF1 leading to increased expression of so-called heat-shock or chaperone proteins that work to maintain protein homeostasis in stressed cells. Scientists have known for some time that many cancer cells have higher levels of chaperones and that elevation of these proteins is important for survival and proliferation of tumor cells.

Now, however, researchers in the lab of Whitehead Member Susan Lindquist report that HSF1 supports cancers not only by increasing chaperones, but by unexpectedly regulating a broad range of cellular functions that are important for the malignant behavior of tumor cells. This activity allows for the development of the most aggressive forms of three of the most prevalent cancersbreast, lung, and colon. The findings, published this week in the journal Cell, build on earlier research from the Lindquist lab showing that elevated levels of HSF1 are associated with poorer prognosis in some forms of breast cancer.

"This work shows that HSF1 is fundamentally important across a broad range of human cancers, cancers of various types from all over the body turn on this response," says Sandro Santagata, a postdoctoral researcher in the Lindquist lab. "
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Contact: Nicole Giese Rura
rura@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

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