Investigation of Mitochondrial Meadiated Cellular Mechanisms In Cancer Progression

Abstract

newline Mitochondria play a vital role in cellular homeostasis as it regulates cell proliferation and death newlinepathways that are attributed to mitochondrial bioenergetics, free radicals and metabolism. newlineAlterations in mitochondrial functions have been reported in various diseases, including cancer. newlineColorectal cancer (CRC) is one of the most common metastatic cancers with high mortality rates. newlineAlthough mitochondrial oxidative stress has been associated with CRC, its specific mechanism newlineand contribution to metastatic progression remain poorly understood. In this study, we newlineinvestigated the role of mitochondria in CRC cells with low and high metastatic potential to newlineexplore the contribution of mitochondrial respiratory chain (RC) complexes in oncogenic newlinesignaling pathways. Our results demonstrated that cell lines with low metastatic potential were newlineresistant to mitochondrial complex I (C-I)-mediated oxidative stress, and showed C-I inhibition newlinewith impaired mitochondrial functions. These adaptations enabled cells to cope with higher newlineoxidative stress. Conversely, cells with high metastatic potential showed functional C-I with newlineimproved mitochondrial function due to coordinated up-regulation of mitochondrial biogenesis newlineand metabolic reprogramming. Pharmacological inhibition of C-I in high metastatic cells resulted newlinein increased sensitivity to cell death and decreased metastatic signaling. Our findings document newlinethe differential regulation of mitochondrial functions in colorectal cancer cells, based on CRC newlinemetastatic potential. Specifically, the findings suggest that a functional C-I is required for high newlinemetastatic behavior of cancer cells, and role of C-I could be further explored as a potential target newlinein the development of novel therapies for diagnosing high metastatic cancers. newlineIn another study we evaluate mt-DNA content among Breast cancer individual. Breast cancer is newlinethe most common and fastest growing cancer worldwide and India attributed due to lack of newlineawareness, non-availability of reliable early diagnosis markers and