The same gene responsible for preventing genetic mutations is also responsible for causing more than half of all types of cancer, and now, scientists from Virginia Commonwealth University and the Van Andel Research Institute in Michigan have found out why.

According to Dr. Richard Moran of the VCU Massey Cancer Center and his colleagues, the gene in question is called p53. Mutations can cause it to activate a protein complex, mTORC1 (aka mammalian target of rapamycin complex 1) which helps regulate the energy resources needed by the body for the process of cell proliferation.

This complex is comprised of dozens of proteins held together by the intracellular membranes of their lysosome, and in response to a typically cell’s need, the p53 gene maintains proper levels of a protein known as tuberous sclerosis complex 2 (TSC2) in the lysosome. However, when p53 is not functioning properly, TCS2 levels in the lysosome begin to decrease.

When this occurs, it is replaced by another type of protein called Ras homolog enriched in brain (RHEB), Dr. Moran’s team explained in the journal Molecular Cancer Research . Accumulation of RHEB activates mTORC1, which in turn causes abnormal cell growth and reproduction.

Possible new uses for the lung cancer drug, Pemetrexed

“We have uncovered for the first time the signaling process that leads to excessive growth of cancer when p53 is lost,” said Dr. Moran, who is the cancer research chair at the Massey Center as well as a pharmacology and toxicology at the VCU School of Medicine.

He added that these protein interactions “are like individual links in the chain of events leading to the development of cancer.” In a separate but similar study, the researchers also found that the cancer drug pemetrexed, which was co-developed by Dr. Moran, could inhibit one of the main controlling compounds of the mTORc1 protein complex, thus halting cell proliferation.

This research showed that the lung cancer medication was effective, regardless of whether or not there were p53 mutations or if the main mTORC1 regulator, TSC2, was no longer functional. He said that the results suggest pemetrexed may have “much greater clinical use” than first thought.

“This research lays the foundation for its use against other cancers in which p53 is not functioning properly, as well as tuberous sclerosis complex, a syndrome driven by loss of TSC2 function that causes disastrous growth of benign but progressive tumors in major organs,” added Dr. Moran, whose work was funded in part by the US National Cancer Institute.

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