Oncology Central

ATM kinase suppresses tumorigenesis by preventing the evasion of senescence, metabolic programming reveals

0
Researchers at The Wistar Institute in Philadelphia (PA, USA) have published new findings in the journal Cell Reports, which reveal evidence of a mechanism cancer cells use to overcome the tumor-supressing metabolic process of senescence. The research reinforces the notion that metabolism is a distinct hallmark of cancer progression.

Senescence, as a metabolic process, prevents cell growth and supresses tumorigenesis in the presence of tumor-promoting metabolic changes. When cells evade senescence, there is an increased potential for the cells to become cancerous.

The study, led by Katherine Aird from the Wistar Insitute, utilized metabolic programming to investigate the potential mechanisms by which cells evade senescence. Aird and her team reported that metabolic reprogramming resulted in the proliferation of cells that should be senescent and such proliferative cells could lead to tumorigenesis.

It is currently known that the protein kinase ataxia telangiectasia mutated (ATM)is mutated in approximately 1 in 50,000 individuals and this confers a 25% lifetime risk of cancer.

More specifically, suppression of ATM was demonstrated to inhibit the tumor suppressor p53 when supressed, as well as augmenting the expression of the c-MYC oncogene, thus promoting cancer.

The timely observations present a novel perspective on how cancers may bypass tumor-supressing metabolic obstacles. Dario C Altieri from The Wistar Institute commented: “The results point the way on how it may be possible to target the unique metabolism of tumor cells for novel therapies.”

Corresponding author Rugang Zhang from The Wistar Institute’s Gene Expression and Regulation Program added, : “A better understanding of the basic regulatory processes that control cancer metabolism is critical for eventually targeting this process for the development of novel cancer therapeutics. With this study, we have found that specific metabolic changes can overcome senescence. We may be able to exploit this for cancer therapy by reversing these senescence-overcoming metabolic changes.”

Discovery could shed light on why many cancers exhibit a ‘loss’ of ATM, and could provide critical insight into why individuals with ATM mutations have an above-average incidence of cancer.

Sources: Aird KM, Worth AJ, Snyder NW et al. ATM Couples Replication Stress and Metabolic Reprogramming during Cellular Senescence. Cell Reports. DOI: 10.1016/j.celrep.2015.04.014 (2015); The Wistar Institute press release

 

Share:

Leave A Comment