title: Mitochondrial Ca(2+) Remodeling is a Prime Factor in Oncogenic Behavior.
abstract: Cancer is sustained by defects in the mechanisms underlying cell proliferation, mitochondrial metabolism, and cell death. Mitochondrial Ca(2+) ions are central to all these processes, serving as signaling molecules with specific spatial localization, magnitude, and temporal characteristics. Mutations in mtDNA, aberrant expression and/or regulation of Ca(2+)-handling/transport proteins and abnormal Ca(2+)-dependent relationships among the cytosol, endoplasmic reticulum, and mitochondria can cause the deregulation of mitochondrial Ca(2+)-dependent pathways that are related to these processes, thus determining oncogenic behavior. In this review, we propose that mitochondrial Ca(2+) remodeling plays a pivotal role in shaping the oncogenic signaling cascade, which is a required step for cancer formation and maintenance. We will describe recent studies that highlight the importance of mitochondria in inducing pivotal "cancer hallmarks" and discuss possible tools to manipulate mitochondrial Ca(2+) to modulate cancer survival.
authors.affiliation: Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), Department of Morphology, Surgery and Experimental Medicine, University of Ferrara , Ferrara , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rimessi
authors.affiliation: Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), Department of Morphology, Surgery and Experimental Medicine, University of Ferrara , Ferrara , Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Patergnani
authors.affiliation: Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), Department of Morphology, Surgery and Experimental Medicine, University of Ferrara , Ferrara , Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bonora
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology , Warsaw , Poland.
authors.forename: Mariusz R
authors.initials: MR
authors.lastname: Wieckowski
authors.affiliation: Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), Department of Morphology, Surgery and Experimental Medicine, University of Ferrara , Ferrara , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
keywords: Ca2+ signaling; cancer; mitochondrial dysfunction; oncogene and oncosuppressor