PRCC-TFE3 regulates migration and invasion of translocation renal cell carcinomas via activation of Drp1-dependent mitochondrial fission.

PRCC-TFE3 translocation renal cell carcinomas (tRCC) is a common subtype of TFE3 tRCCs in which TFE3 fusions are indicated as oncogenes to promote tumor development. PRCC-TFE3 fusions are often accumulated in the nucleus and related to poorer outcomes and higher stages (III/IV). In this study, we found that PRCC-TFE3 could positively regulate expression of both dynamin-related protein 1 (Drp1) and fission protein 1, and alter distribution of mitochondria, which could promote cell migration and invasion independent of matrix metalloproteinase-2 (MMP-2) and MMP-9. Together, our findings showed a new mechanism for PRCC-TFE3 tRCC cell migration and invasion by alteration of mitochondrial dynamics. Thus, targeting dysregulated Drp1-dependent mitochondrial fission may provide a novel strategy for suppressing the progression of PRCC-TFE3 tRCC.