c-Src functionality controls self-renewal and glucose metabolism in MCF7 breast cancer stem cells

PloS One
Víctor Mayoral-VaroJorge Martín-Pérez

Abstract

Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells reduces tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of Breast Cancer Stem Cells (BCSCs) from MCF7 cells with inducible expression of SrcDN. Induction of SrcDN inhibited self-renewal, and stem-cell marker expression (Nanog, Oct3-4, ALDH1, CD44). Quantitative proteomic analyses of mammospheres from MCF7-Tet-On-SrcDN cells (data are available via ProteomeXchange with identifier PXD017789, project DOI: 10.6019/PXD017789) and subsequent GSEA showed that SrcDN expression inhibited glycolysis. Indeed, induction of SrcDN inhibited expression and activity of hexokinase, pyruvate kinase and lactate dehydrogenase, resulting in diminished glucose consumption and lactate production, which restricted Warburg effect. Thus, c-Src functionality is important for breast cancer stem cell maintenance and renewal, and stem cell transcription factor expression, effects linked to glucose metabolism reduction.

References

Mar 1, 1994·Molecular and Cellular Biology·M D SchallerJ T Parsons
Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Sep 13, 2005·Cell·Laurie A BoyerRichard A Young
Jan 6, 2006·Nature·John StinglConnie J Eaves
Jan 7, 2006·Nature·Mark ShackletonJane E Visvader
May 27, 2006·The Journal of Biological Chemistry·Lorena GonzálezJorge Martín-Pérez
Nov 30, 2007·Anti-cancer Agents in Medicinal Chemistry·Faye M Johnson, Gary E Gallick
Mar 1, 2008·The Journal of Biological Chemistry·Cristina AdánRafael Garesse
May 20, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R S Finn
Jan 27, 2009·Current Opinion in Genetics & Development·Lauren L Campbell Marotta, Kornelia Polyak
Jul 4, 2009·Cancer Cell·Xiang H-F ZhangJoan Massagué
Jul 8, 2009·The Oncologist·Deric L WheelerEmily F Dunn
Nov 7, 2009·Cellular Signalling·José Manuel García-MartínezJorge Martín-Pérez
Nov 27, 2009·The Journal of Biological Chemistry·Natasha R SchuhAmy H Bouton
Aug 7, 2010·Neoplasia : an International Journal for Oncology Research·Alexey Aleshin, Richard S Finn
Apr 22, 2011·Nature Reviews. Cancer·Willem H KoppenolChi V Dang
Sep 3, 2011·Breast Cancer Research : BCR·Deborah L Holliday, Valerie Speirs
May 10, 2012·Cellular Signalling·María Pilar Sánchez-BailónJorge Martín-Pérez
Mar 4, 2014·The Biochemical Journal·Lucía EchevarríaRafael Garesse
Dec 22, 2014·Cancer Letters·Katarzyna AugoffRenata Tabola
Nov 3, 2015·Nature·Ayuko HoshinoDavid Lyden
Nov 23, 2015·Molecular Cell·Gina M DeNicola, Lewis C Cantley
Feb 16, 2016·Cell Reports·Candice Sun HongHeather R Christofk
Aug 4, 2016·Nature Communications·Ji LiangZhimin Lu
Mar 23, 2017·International Review of Cell and Molecular Biology·J Espada, J Martín-Pérez
Nov 29, 2017·PloS One·Víctor Mayoral-VaroJorge Martín-Pérez
Jul 19, 2018·Biomedicines·Judy S Crabtree, Lucio Miele
Nov 6, 2018·Nucleic Acids Research·Yasset Perez-RiverolJuan Antonio Vizcaíno
Feb 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Dongya JiaHerbert Levine

❮ Previous
Next ❯

Citations

Dec 15, 2020·World Journal of Stem Cells·Xu Gao, Qiong-Zhu Dong
Oct 15, 2020·International Journal of Molecular Sciences·Sonia AlcaláBruno Sainz

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
transfection
FACS
protein assay
fluorescence-activated cell sorting
Assay
flow cytometry

Software Mentioned

Excel
GSEA
ImageJ
GeneMapper
Mascot Server

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Cancer Metabolic Reprogramming (Keystone)

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Cancer Metabolic Reprogramming

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Related Papers

The Journal of Biological Chemistry
Lorena GonzálezJorge Martín-Pérez
Neoplasma
A SoltysovaC Altaner
Recent Patents on DNA & Gene Sequences
Wei Wu
Breast Cancer Research and Treatment
Jessica C LawsonAdrienne L Edkins
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Chiranjib ChakrabortySrijit Das
© 2021 Meta ULC. All rights reserved