Researchers have identified a new signalling pathway that enables cancer cells to survive despite the low oxygen levels found inside tumours.
This is according to the results of a study led by researchers at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center, Princess Margaret Cancer Center, the University of Toronto, Harvard Medical School and Oxford University.
Human cells require oxygen to thrive, however cancer cells survive even when deprived of it. The abnormal and rapid cell growth seen in many solid tumours causes them to outgrow their blood supply, leaving some cells with little oxygen. This is known as hypoxia, and when faced with it, cancer cells change their gene expression to turn off all but the most vital oxygen-using processes.
The researchers found that signals sent by the enzyme protein-tyrosine phosphatase 1B (PTP1B) work in a previously unknown way to shut down oxygen-using processes in breast cancer cells deprived of oxygen, therefore enabling their survival.
PTP1B is the hallmark member of a group of enzymes that take a phosphate group away from biomolecules to turn processes including cell growth on or off. The gene for PTP1B was first identified in the early 1990s as part of a search for molecules that suppress tumour growth.
In the new research, the scientists found that PTP1B controls the response of tumours in hypoxia by regulating the protein RNF213, which in in turn suppresses oxygen consumption by enzymes (α-ketoglutarate-dependent dioxygenases (α-KGDDs)). These enzymes use oxygen, vitamin C (ascorbic acid) and iron to catalyse a number of reactions.
Dr Benjamin Neel, PhD, director of the Perlmutter Cancer Center, said: “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.”