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Selective Vulnerability of Cancer Cells by Inhibition of Ca(2+) Transfer from Endoplasmic Reticulum to Mitochondria.

Abstract：

:In the absence of low-level ER-to-mitochondrial Ca(2+) transfer, ATP levels fall, and AMPK-dependent, mTOR-independent autophagy is induced as an essential survival mechanism in many cell types. Here, we demonstrate that tumorigenic cancer cell lines, transformed primary human fibroblasts, and tumors in vivo respond similarly but that autophagy is insufficient for survival, and cancer cells die while their normal counterparts are spared. Cancer cell death is due to compromised bioenergetics that can be rescued with metabolic substrates or nucleotides and caused by necrosis associated with mitotic catastrophe during their proliferation. Our findings reveal an unexpected dependency on constitutive Ca(2+) transfer to mitochondria for viability of tumorigenic cells and suggest that mitochondrial Ca(2+) addiction is a feature of cancer cells.

journal_name

Cell Rep

journal_title

Cell reports

authors

Cárdenas C,Müller M,McNeal A,Lovy A,Jaňa F,Bustos G,Urra F,Smith N,Molgó J,Diehl JA,Ridky TW,Foskett JK

doi

10.1016/j.celrep.2016.02.030

subject

Has Abstract

pub_date

2016-03-15 00:00:00

pages

2313-24

issue

10

issn

2211-1247

pii

S2211-1247(16)30133-4

journal_volume

14

pub_type

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