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Trends Cancer. 2017 Nov;3(11):768-779. doi: 10.1016/j.trecan.2017.09.002. Epub 2017 Oct 17.

Mitochondrial OXPHOS Induced by RB1 Deficiency in Breast Cancer: Implications for Anabolic Metabolism, Stemness, and Metastasis.

Author information

1
Division of Advanced Diagnostics, Toronto General Research Institute, University Health Network, 67 College Street, Toronto, ONT M5G 2M1, Canada; Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ONT ​ M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, ONT M5G 2C4, Canada. Electronic address: eldad.zacksenhaus@utoronto.ca.
2
Division of Advanced Diagnostics, Toronto General Research Institute, University Health Network, 67 College Street, Toronto, ONT M5G 2M1, Canada; Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ONT ​ M5S 1A8, Canada.
3
Division of Advanced Diagnostics, Toronto General Research Institute, University Health Network, 67 College Street, Toronto, ONT M5G 2M1, Canada.
4
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.

Abstract

A switch from catabolic to anabolic metabolism, a major hallmark of cancer, enables rapid cell duplication, and is driven by multiple oncogenic alterations, including PIK3CA mutation, MYC amplification, and TP53 loss. However, tumor growth requires active mitochondrial function and oxidative phosphorylation (OXPHOS). Recently, loss of the retinoblastoma (RB1) tumor suppressor in breast cancer was shown to induce mitochondrial protein translation (MPT) and OXPHOS. Here, we discuss how increased OXPHOS can enhance anabolic metabolism and cell proliferation, as well as cancer stemness and metastasis. Mitochondrial STAT3, FER/FER-T, and CHCHD2 are also implicated in OXPHOS. We propose that RB1 loss represents a prototypic oncogenic alteration that promotes OXPHOS, that aggressive tumors acquire lethal combinations of oncogenes and tumor suppressors that stimulate anabolism versus OXPHOS, and that targeting both metabolic pathways would be therapeutic.

KEYWORDS:

anabolic metabolism; breast cancer; cancer stem cell; glycolysis; metastasis; mitochondrial protein translation; oxidative phosphorylation; tumor suppressor RB1

PMID:
29120753
DOI:
10.1016/j.trecan.2017.09.002
[Indexed for MEDLINE]

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