"Energetic" Cancer Stem Cells (e-CSCs): A New Hyper-Metabolic and Proliferative Tumor Cell Phenotype, Driven by Mitochondrial Energy

Frontiers in Oncology
Marco FiorilloMichael P Lisanti

Abstract

Here, we provide the necessary evidence that mitochondrial metabolism drives the anchorage-independent proliferation of CSCs. Two human breast cancer cell lines, MCF7 [ER(+)] and MDA-MB-468 (triple-negative), were used as model systems. To directly address the issue of metabolic heterogeneity in cancer, we purified a new distinct sub-population of CSCs, based solely on their energetic profile. We propose the term "energetic" cancer stem cells (e-CSCs), to better describe this novel cellular phenotype. In a single step, we first isolated an auto-fluorescent cell sub-population, based on their high flavin-content, using flow-cytometry. Then, these cells were further subjected to a detailed phenotypic characterization. More specifically, e-CSCs were more glycolytic, with higher mitochondrial mass and showed significantly elevated oxidative metabolism. e-CSCs also demonstrated an increased capacity to undergo cell cycle progression, as well as enhanced anchorage-independent growth and ALDH-positivity. Most importantly, these e-CSCs could be effectively targeted by treatments with either (i) OXPHOS inhibitors (DPI) or (ii) a CDK4/6 inhibitor (Ribociclib). Finally, we were able to distinguish two distinct phenotypic sub-types of e-CS...Continue Reading

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Citations

Jul 6, 2019·Carcinogenesis·Anastasia KariaginaJ Justin McCormick
Sep 5, 2020·Cancers·Samson Mathews SamuelDietrich Büsselberg
Apr 4, 2019·Frontiers in Oncology·Catherine Vander Linden, Cyril Corbet
Jul 15, 2020·Cells·María Auxiliadora Olivares-UrbanoMaría Isabel Núñez
Mar 27, 2020·Frontiers in Oncology·Dayanidhi RamanJulie A Rhoades Sterling
Nov 5, 2019·Frontiers in Oncology·Sangita SridharanDayanidhi Raman
Sep 8, 2019·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Teodora Alexa-StratulatChiara Riganti
May 20, 2020·Seminars in Cancer Biology·Félix A Urra, Ramiro Araya-Maturana
Feb 22, 2021·Cytokine & Growth Factor Reviews·Francesca De SantisMassimo Di Nicola
May 29, 2021·Clinical and Experimental Pharmacology & Physiology·Da-Yong ZhangWen-Yi Gu
Oct 10, 2021·BMC Cancer·Zane SimsoneIndulis Buiķis
Nov 11, 2021·Mitochondrion·Shalini ManiStephen J Ralph

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Methods Mentioned

BETA
flow-cytometry
FACS
Assay

Software Mentioned

XFe96
GraphPad Prism
IPA
M - plotter
SONY Cell

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