A study from researchers at The Children’s Hospital of Philadelphia may add new lines to the textbook description of how cancer cells divide uncontrollably and develop into tumors.
The finding, published in Nature Communications, could directly apply to multiple cancer types because it describes a molecular interaction that is part of the Rb pathway, which is common in many cancers.
Part of that pathway involves a family of proteins that are steadily turned on in cancer, called E2f transcription factors. The known role of these E2f proteins is to help to either activate or deactivate expression of certain genes to regulate how cells divide. (Known as the cell cycle, this process is a normal part of growth but proceeds out of control in cancer.) In this process, the E2f proteins activate or deactivate certain genes by binding to specific target regions of DNA.
The CHOP team found a molecular mechanism that links the accumulation of too much of one of these E2f proteins in cancer to other characteristic features of cancer cells. The protein E2f1 is frequently overactive in late-stage cancers and is linked to poor prognoses. Accumulated quantities of E2f1 ultimately activate many more genes than just the textbook-standard ones it was known to activate as part of the cell cycle, according to Patrick Viatour, PharmD, PhD, the study’s senior author, an investigator at CHOP and assistant professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania.
In particular, some of these other activated genes regulate a process that rewires the energy metabolism in cancer cells for rapid growth. Dr. Viatour and colleagues believe many more genes are activated by this amplification mechanism, as well. They suggest that the mechanism could be a central hub connecting excess cell proliferation together with other characteristic features of cancer cells that collectively make up the process of tumor formation.
See the full version of this article in the January 2016 issue of Bench to Bedside.