Mitochondrial metabolism: Yin and Yang for tumor progression

Altered metabolism is a distinct feature of cancer cells. During transformation, the entire metabolic network is rewired to efficiently convert nutrients to biosynthetic precursors to sustain cancer cell growth and proliferation. Whilst the molecular underpinnings of this metabolic reprogramming have been described, its role in tumor progression is still under investigation. Importantly, the mitochondrion is a central actor in many of the metabolic processes that are altered in tumors. Yet, we have only begun to understand the dualities of mitochondrial function during cancer metastasis and therapy resistance. Paradoxically, mitochondrial metabolism can be both advantageous and detrimental to these processes, highlighting the need for a better understanding of the molecular and microenvironmental cues that define the role of this fascinating organelle. In this review article, we present an updated view on the different mitochondrial metabolic strategies adopted by cancer cells to overcome the many hurdles faced during tumor progression.The work of A.C. is supported by the Ramón y Cajal award, the Basque Department of Industry, Tourism and Trade (Etortek) and the Department of Education (IKERTALDE IT1106-16), ISCIII (PI10/01484, PI13/00031), FERO VIII Fellowship, the BBVA Foundation, the MINECO (SAF2016-79381-R), and the European Research Council Starting Grant (336343). The participation of A.C. and V.T. as part of CIBERONC was cofunded with FEDER funds. L.V-J. is supported by Basque Government of Education. V.T. is funded by Fundación Vasca de Innovación e Investigación Sanitarias, BIOEF (BIO15/CA/052), the AECC J.P. Bizkaia, and the Basque Department of Health (2016111109). E.G. and C.F. are supported by the Medical Research Council, core fund to the MRC Cancer Unit SKAG106