In a recent study published in Cancer Cell titled “Rab1A Is an mTORC1 Activator and a Colorectal Oncogene”, a team of researchers from the Rutgers Cancer Institute, New Jersey, has shown that, Rab1A, a small GTPase enzyme, is an essential switch for amino acid signalling. This in turn can prove to play an important role in the development of colorectal cancer and targeted cancer therapies.
Rab1A GTPase enzyme is part of the mTORC1 protein complex, a key regulator of cell growth and metabolism. When this enzyme senses the presence of amino acids, it stimulates Rheb, another GTPase, to activate the mTORC1 pathway on the Golgi apparatus, which is responsible for trafficking proteins within the cell.
In the study, researchers showed that Rab1A is a conserved regulator of amino acid signaling to mTORC1 and it is commonly overexpressed in colorectal cancer, stimulating mTORC1 signaling and oncogenic growth in an amino acid and mTORC1-dependent manner. This in turn promotes tumor invasion, progression, and poor prognosis.
The exact role of amino acids in human diseases remains a question to be answered. This study reveals the first important evidence that abnormal upregulation of amino acid signaling can be linked to cancer growth and development.
Additionally, researchers found that knocking down Rab1A attenuated the oncogenic growth of Rab1-overexpressing cancer cells.
Furthermore, if cells had enhanced levels of Rab1A, they were more prone to rapamycin, a drug responsible for blocking the growth-stimulating effect of mTORC1.
Knowing that tumors overproducing Rab1A are more aggressive opens up the possibility of using it as a surrogate biomarker to improve clinical diagnosis and predict the outcome of mTORC1-targeted cancer therapy.
“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,” noted study author X.F. Steven Zheng, PhD, co-leader of the Cancer Pharmacology and Preclinical Therapeutics Program at the Cancer Institute of New Jersey and a university professor of pharmacology at Rutgers Robert Wood Johnson Medical School.