Newly Identified Oncogene Links Amino Acids to Colorectal Cancer Development
By LabMedica International staff writers Posted on 02 Nov 2014 |
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.”
Related Links:
Rutgers University
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.”
Related Links:
Rutgers University
Latest BioResearch News
- Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns
- Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma
- New Method Simplifies Preparation of Tumor Genomic DNA Libraries
- New Tool Developed for Diagnosis of Chronic HBV Infection
- Panel of Genetic Loci Accurately Predicts Risk of Developing Gout
- Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria
- Gene Fusion Protein Proposed as Prostate Cancer Biomarker
- NIV Test to Diagnose and Monitor Vascular Complications in Diabetes
- Semen Exosome MicroRNA Proves Biomarker for Prostate Cancer
- Genetic Loci Link Plasma Lipid Levels to CVD Risk
- Newly Identified Gene Network Aids in Early Diagnosis of Autism Spectrum Disorder
- Link Confirmed between Living in Poverty and Developing Diseases
- Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients
- Liquid Biopsy More Effective for Analyzing Tumor Drug Resistance Mutations
- New Liquid Biopsy Assay Reveals Host-Pathogen Interactions
- Method Developed for Enriching Trophoblast Population in Samples