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Cancer and senescence.

Cancer and senescence.

Publish date: 2013-05-28

Cancer experts from Denmark have found an enzyme that seems to induce cancer senescence.

Tags: medicine , cancer

When oncogenes are activated inside a cell, they normally mobilise neoplasm suppressor networks which can act like a brake to cancer through a process termed oncogene-induced senescence (OIS). They depart proliferating cells almost irreversibly, ensuring protection against vicious transformation. Now, a research team led by Daniel Peeper from the Netherland’s Cancer Institute in Amsterdam has identified a metabolic gate-keeper of the process.

Using metabolic and functional analyses of melanoma cells carrying the common BRAFV600E mutation, the team of Dutch, Scottish, Belgian, Spanish, Israeli and US scholars identified the TCA enzyme pyruvate dehydrogenase  (PDH) as arevelant mediator of cancer senescence. BRAFV600E-entailed senescence was accompanied by simultaneous  suppression of the PDH-inhibitory enzyme pyruvate dehydrogenase kinase 1 (PDK1) and induction of the PDH-activating enzyme pyruvate dehydrogenase phosphatase 2 (PDP2). The total combined activation of PDH enhanced the use of pyruvate in the tricarboxylic acid cycle, causing increased respiration and redox stress.

Exacted standardization of either PDK1 or PDP2 expression horizon inhibited PDH and abrogated oncogene-induced senescence. Diminution of PDK1 eradicated melanoma subpopulations proof to targeted BRAF inhibition, and caused regression of established melanomas. The results suggest a mechanistically new therapeutic way to induce cancer senescence and stop growth cell proliferation at its earliest stages.

 

Source: http://www.eurobiotechnews.eu [http://www.eurobiotechnews.eu/news/news/2013-02/metabolic-gatekeeper-to-cancer-senescence.html]

 

edited by Agnieszka Dąbrowska

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