ER-mitochondria interactions: Both strength and weakness within cancer cells
Mabrouka Doghman-Bouguerra1, Enzo Lalli1
1Université Côte d'Azur, Valbonne 06560, France; CNRS UMR 7275, Sophia Antipolis, Valbonne 06560, France; EXPOGEN-CANCER CNRS International Associated Laboratory, Valbonne 06560, France; Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne 06560, France.
Abstract:
ER-mitochondria contact sites represent hubs for signaling that control mitochondrial biology related to several aspects of cellular survival, metabolism, cell death sensitivity and metastasis, which all contribute to tumorigenesis. Altered ER-mitochondria contacts can deregulate Ca2+ homeostasis, phospholipid metabolism, mitochondrial morphology and dynamics. MAM represent both a hot spot in cancer onset and progression and an Achilles' heel of cancer cells that can be exploited for therapeutic perspectives. Over the past years, an increasing number of cancer-related proteins, including oncogenes and tumor suppressors, have been localized in MAM and exert their pro- or antiapoptotic functions through the regulation of Ca2+ transfer and signaling between the two organelles. In this review, we highlight the central role of ER-mitochondria contact sites in tumorigenesis and focus on chemotherapeutic drugs or potential targets that act on MAM properties for new therapeutic approaches in cancer.
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