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Mechanism of Cancer Cells Survival in Hypoxic Condition Revealed

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Researchers at the New York University Langone Medical Centre and its Laura and Perlmutter Cancer Centre have uncovered a previously unknown signalling pathway through which cancer cells thrive despite the lack of oxygen inside tumors.

The research group headed by Dr. Benjamin Neel, MD, PhD, director of the Perlmutter Cancer Centre, published their findings in Nature Cell Biology on June 20th, 2016.

With the results obtained, they hope to facilitate the design of treatment methods wherein cancer cells are drawn into a hypoxic condition and their mechanism of coping with the lack of oxygen is disrupted.

The below video explains how breast cancer spread are triggered by the low oxygen levels in tumor cells (Video credit: EmpoweredDoctor).

All cells in the human body require oxygen for various cellular processes. However, it has been observed that cancer cells can somehow circumvent the need for oxygen and thrive even in its absence. This has baffled researchers for several years and research in cancer treatment mainly involved finding the pathways that cancer cells use to adapt to lower levels of oxygen.

hypoxia trigger cancer growth

Figure 1. MITF-directed regulation of HIF in normal and cancer cells (photo credit: Nat Med. 2012 Jan 6;18(1):30-1. doi: 10.1038/nm.2631).

In his study, they found that the enzyme protein-tyrosine phosphatase 1B (PTP1B) was responsible for shutting down processes that utilize oxygen, thereby enhancing the survival of the tumour cells.

PTP1B belongs to a group of enzymes that are capable of turning on and off various processes in the body, such as cell division, by the mechanism of removal of a phosphate group from the biomolecules involved.

role of PTP1B in cancer

Figure 2. Role of PTP1B in cancer (photo credit: Trends Biochem Sci. 2010 Aug;35(8):442-9. doi: 10.1016/j.tibs.2010.03.004.).

In earlier studies carried out by Dr. Neel and his colleagues, it was found that PTP1B could play a role in the growth of certain cancers.

In this study, it was found that PTP1B controlled tumor response to hypoxia through the regulation of a protein RNF213, which in turn suppresses oxygen consumption by alpha ketoglutarate dependent dioxygenases.

The potential for this line of research is far reaching. In addition to its use in cancer therapy, the role of PTP1B and RNF213 in Moyamoya disease pathogenesis may also be explored which results in abnormal blood vessel growth in the brain.

We have seen many times in the cancer field that studies of rare syndromes can be being important in explaining mechanisms by which cells respond to stresses,” says Neel. “We hope our new study will provide insights into Moyamoya disease that then feed back into our work in cancer biology“.

Featured image credit: 3D computer generated microscope close up of cancer cell. © vitanovski (Stock Photo ID: 93981836)

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