Roles of mitochondria in the hallmarks of metastasis

Although mitochondrial contributions to cancer have been recognised for approximately a century, given that mitochondrial DNA (mtDNA) is dwarfed by the size of the nuclear genome (nDNA), nuclear genetics has represented a focal point in cancer biology, often at the expense of mtDNA and mitochondria. However, genomic sequencing and advances in in vivo models underscore the importance of mtDNA and mitochondria in cancer and metastasis. In this review, we explore the roles of mitochondria in the four defined 'hallmarks of metastasis': motility and invasion, microenvironment modulation, plasticity and colonisation. Biochemical processes within the mitochondria of both cancer cells and the stromal cells with which they interact are critical for each metastatic hallmark. We unravel complex dynamics in mitochondrial contributions to cancer, which are context-dependent and capable of either promoting metastasis or being leveraged to prevent it at various points of the metastatic cascade. Ultimately, mitochondrial contributions to cancer and metastasis are rooted in the capacity of these organelles to tune metabolic and genetic responses to dynamic microenvironmental cues.

Automated summary

Mitochondria play crucial roles in cancer and metastasis, particularly in aspects such as motility, invasion, microenvironment modulation, plasticity, and colonisation. While nuclear genetics has traditionally been the focus in cancer biology, the importance of mitochondria and mtDNA is gaining recognition. The complex dynamics of mitochondrial contributions to cancer can either promote or prevent metastasis, depending on the context.