Cancer Cells Chill Out to Survive

20 September 2007 (All day)

Cancer cells are tough little devils. Even though they endure starvation, oxygen shortages, and pummeling from the immune system, they continue to divide out of control. New research chalks this resilience up to a protein that shields healthy cells from stress--a finding that tags the protein as a potential target for future antitumor drugs.

When cells are under duress, heat shock proteins (HSPs) get busy. By preventing other proteins from folding incorrectly or congregating into potentially hazardous clumps, these molecular guardians may help stave off neurodegenerative disorders such as Parkinson's disease. Orchestrating the HSPs is a take-charge protein called heat shock factor 1 (HSF1). Like other cells, cancer cells boost their production of HSPs in response to stress, but whether they use HSF1 to call the shots wasn't certain.

To find out, molecular biologist Susan Lindquist of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and colleagues dabbed mice with cancer-inducing chemicals. More and larger skin tumors sprouted in animals lacking HSF1 than in controls, the scientists report in the 21 September issue of Cell. The researchers also tested how the loss of HSF1 affected mouse cells carrying either of two cancer-inducing mutant genes. If the cells could make HSF1, they divided rapidly and piled up on the culture dish. HSF1-deficient cells, by contrast, rarely formed these mounds. Those results suggest that HSF1 is necessary for cells to become cancerous.

The protein is also essential for tumor cells to remain alive and multiply. Slashing the amount of HSF1 in several lines of human cancer cells diminished growth and survival. What's more, loss of the protein hampers two adjustments--increased glucose intake and protein production--that help cancer cells maintain their rapid division, the team found.

HSF1 isn't a cause of cancer, it's an enabler, mobilizing defenses that permit the cells to survive under harsh conditions, the researchers conclude. Co-author Luke Whitesell, a pediatric oncologist at the Whitehead Institute, says that the protein puts organisms in a bind: "HSF1 enhances survival and stress tolerance, but there appears to be a flip side in cancer." That duality could complicate the use of HSF1 inhibitors--which the researchers are now hunting for--to combat tumors. However, Whitesell says, short, intense treatments with such drugs might stall cancer without leaving patients vulnerable to neurodegeneration and other disorders caused by cell stress.

The work "shows a clear role for HSF1 in cancer," says molecular biologist Stuart Calderwood of Harvard Medical School in Boston. Cell biologist Nahid Mivechi of the Medical College of Georgia in Augusta agrees that the results are "very significant." HSF1 controls other genes besides those for HSPs, so researchers now need to pin down which molecular mechanisms the protein enlists to help cancer cells beat stress, says Calderwood.

Related sites

Posted In: