Mitochondria and metastasis. Role of ERRalpha in colon cancer

Abstract

[eng] ERRα targets genes implicated in the regulation of the mitochondrial networking: mitochondrial dynamics and mitochondrial biogenesis. Mitochondrial networking is related to progression and malignancy in cancer. The complete role of ERRα in mitochondrial networking in colon cancer is yet unclear. Furthermore, it has been shown that mitochondrial networking participates in metastasis. Therefore, we aimed to analyze gene levels related to mitochondrial networking and metastasis in SW620 colon cancer cells, after ERRα knockdown (siRNA), using RT-qPCR. We found a decrease in mitochondrial biogenesis (TFAM) and mtOXPHOS (ATP5F1A), a decrease in mitochondrial fusion (MFN1), and an increase in mitochondrial fission (DRP1). Regarding EMT, we observed a decrease in TGF-ß and increases in SNAIL and SLUG. Besides, no significant changes were found in stem cell markers or EMT effectors. These findings could indicate that ERRα knockdown promotes a more aggressive and apoptosis-resistant phenotype, despite reducing colon cancer cell growth. ERRα knockdown did enhance EMT only in combination with the chemotherapeutic drug oxaliplatin.