Researchers find pathway that helps cancer cells handle low oxygen levels

Lab work

A group of international researchers have found a new signaling pathway that helps certain cancerous cells survive even without oxygen--a discovery they hope could yield new treatments in the future.

The researchers, from the U.S., Canada and the U.K., published their study this week in Nature Cell Biology.

Oxygen is necessary for healthy cells but a number of studies over the years have shown that cancer cells can exist even in very low oxygen levels--which is necessary for its rapid growth as it can outstrip the blood supply it has been using.

Cancer cells in this state, called hypoxia, can change their gene expression to turn off all but the most vital oxygen-using processes. Until now, it wasn't known how they managed to do this. 

But in their new research, the investigators found that signals sent by the enzyme protein-tyrosine phosphatase 1B (PTP1B) work in a previously unknown way to shut down the oxygen-using processes in breast cancer cells deprived of oxygen--something that increases their survival.

"Our results, by yielding a new understanding of cancer cell response to hypoxia, hopefully will enable the design of future treatments that drive such cells into low-oxygen environments and then take away their ability to survive these conditions," says Benjamin Neel, director of the Perlmutter Cancer Center, in a university release.

Back in the 1990s, Neel helped first identify the gene for protein-tyrosine phosphatase 1B (PTP1B) as part of a search for molecules that overpower tumor growth.

“PTP1B is the hallmark member of a group of enzymes that take a phosphate group away from biomolecules to turn processes like cell growth on or off,” Neel explained.

This comes after Neel and his colleagues found in earlier studies of mice that PTP1B function was necessary for the growth of certain cancers.

These included breast cancers caused by the HER2+ breast cancer cells--which is found in around a quarter of all breast cancers. A number of drugs, including Roche’s ($RHHBY) Herceptin, are currently marketed to deal with these types of breast cancers--and it used to be one of the more difficult to treat subtypes of the disease.

In their more recent work, some of the researchers found that these HER2+ breast cancer cells lacking PTP1B grew normally under standard culture conditions--but died much more rapidly in low oxygen.

They also found that the three signaling pathways by which cancer cells were known to adapt to hypoxia worked fine in PTP1B-deficient HER2+ breast cancer cells.

“These included the well-known hypoxia-inducible factor pathway, which shifts the way cells use oxygen from oxidative phosphorylation in cellular ‘machines’ called mitochondria to glycolysis, which does not require oxygen,” the researchers said in the release.

- here's the release
- check out the Nature Cell Biology paper

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