Newly Identified Oncogene Links Amino Acids to Colorectal Cancer Development

Cancer researchers have identified a novel oncogene—and possible drug target—that promotes development of colorectal cancer by interacting with amino acids to activate the pro-cancer mTORC1 signaling complex.

mTOR (mammalian target of rapamycin) is a master regulator of protein synthesis that under ordinary conditions induces cells to grow and divide. In situations of severe nutrient deprivation mTOR closes down protein synthesis so that the cell can conserve energy. However, in cancer cells the mTOR pathway misfires and signals tumor cells to grow, divide, undergo metastasis, and invade new, healthy tissues.

Investigators at Rutgers University (New Brunswick, NJ, USA) have been looking at the interaction between amino acids and the small GTPase enzyme Rab1A, which is a key switch for amino acid signaling.

They reported in the October 13, 2014, online edition of the journal Cancer Cell that amino acids activated Rab1A, which then stimulated Rheb (another small GTPase) to interact with the mTORC1 complex in the cells' Golgi apparatus. They found that Rab1A overexpression promoted mTORC1 signaling and oncogenic growth in an amino acid- and mTORC1-dependent manner. Blocking Rab1A activity selectively inhibited oncogenic growth of Rab1-overexpressing cancer cells. Furthermore, Rab1A was found to be overexpressed in colorectal cancer, which was correlated with elevated mTORC1 signaling, tumor invasion, progression, and poor prognosis. In contrast, overexpression of Rab1A increased sensitivity of cancer cells toward the drug rapamycin, which blocks the growth-stimulating effect of mTORC1.

Senior author Dr. X. F. Steven Zheng, professor of pharmacology at Rutgers University, said, “In further elucidating the role Rab1A plays in amplifying amino acid signaling, we can further understand this impact on the mTORC1 protein. Especially since elevated levels of mTORC1 signaling is found in colorectal cancer, new therapy options targeted toward mTORC1 can be explored.”

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