Chtm1, A Novel Protein Linked To Cellular Metabolism And Human Malignancy

Several lines of emerging evidence indicate that alterations in metabolism are linked to pathogenesis of human malignancies. However, more studies are needed to completely understand the link between tumorigenesis and metabolism. In this context, we have characterized a novel protein named CHTM1 (Coiled-coil Helix Tumor and Metabolism 1) that appears to be associated with cancer and cellular metabolism. Per our findings, CHTM1 was present in cytosol as well as mitochondria. CHTM1 knockdown in human cancer cell lines caused oxidative stress, and decrease in cellular oxygen consumption and mitochondrial ATP levels, suggesting mitochondrial dysfunction. In view of the importance of mitochondria to nutrient stress, the effect of CHTM1 deficiency on human cancer cells in glucose-deprived conditions was also analyzed. The results indicated that CHTM1-deficient cells became more sensitive to glucose deprivation and exhibited altered cellular metabolism involving down regulation of PKC-CREB-PGC1 alpha signaling events. CHTM1 expression was also found to be increased in patient samples representing breast, colon and lung cancers when compared to their respective matching normal tissues. Based on our findings, we propose CHTM1 to be a valuable tumor marker that can also be developed as a target for novel therapeutics particularly those that exploit cellular metabolism to mediate their effects. Citation Format: Mansi Babbar, Ying Huang, M Saeed Sheikh. CHTM1, a novel protein linked to cellular metabolism and human malignancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4402. doi:10.1158/1538-7445.AM2017-4402