ROLE OF MITOCHONDRIAL CALCIUM IN EMBRYONAL RHABDOMYOSARCOMA

Abstract

Embryonal rhabdomyosarcoma (ERMS) cells are vulnerable to oxidative stress. However, the relevance of mitochondrial calcium homeostasis in oncogenesis is unclear. To address this gap, I analysed the role of the Mitochondrial Calcium Uniporter (MCU) complex in ERMS. I found that MCU is overexpressed whereas MICU1 expression is downregulated in ERMS. MCU knockdown impaired mitochondrial calcium uptake, reactive oxygen species (mROS) production and resulted in reduced proliferation and increased myogenic differentiation in vivo and in vitro. Interestingly, TGFβ signalling was impaired downstream of mROS alterations in MCU knockdown cells. This study elucidates mechanisms by which mitochondrial calcium dysregulation promotes tumour progression.