Oxidized ATM-mediated glycolysis enhancement in breast cancer-associated fibroblasts contributes to tumor invasion through lactate as metabolic coupling

EBioMedicine
Kexin SunManran Liu

Abstract

Cancer-associated fibroblasts (CAFs) are the predominant residents in the breast tumor microenvironment. In our work, we found activation of DNA damage-independent ATM (oxidized ATM), enhanced glycolysis and aberrant metabolism-associated gene expressions in breast CAFs. Nevertheless, whether and how oxidized ATM regulates the glycolytic activity of CAFs keep in unveil. Recently, a reverse Warburg effect was observed in tumor tissues, in which host cells (such as CAFs, PSCs) in the tumor microenvironment have been found to "fuel" the cancer cells via metabolites transfer. However, the molecular mechanisms of the metabolites from stromal cells playing a role to the progression of cancer cells remain to be determined. Oxidized ATM activation in stromal CAFs was assessed by western blotting and immunofluorescence. The increased glycolytic ability of CAFs was validated by measurements of OCR and ECAR and detections of glucose consumption and lactate production. Kinase assay and western blotting were performed to confirm the phosphorylation of GLUT1. The membrane location of phosphorylated GLUT1 was determined by biotin pull-down assay and immunofluorescence staining. The regulation of PKM2 through oxidized ATM was evaluated by west...Continue Reading

References

May 10, 1996·The Journal of Biological Chemistry·R DauteriveB C Reed
Sep 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·S MatsuokaS J Elledge
Oct 30, 2001·Molecular Membrane Biology·P W Hruz, M M Mueckler
Apr 7, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Masahiko KobayashiKen-ichi Yamamoto
Nov 2, 2004·Nature Reviews. Cancer·Robert A Gatenby, Robert J Gillies
May 27, 2005·Molecular Cell·Anindita BhoumikZe'ev Ronai
Feb 17, 2007·The FEBS Journal·Rafael Moreno-SánchezEmma Saavedra
Nov 5, 2008·Molecular and Cellular Biology·Zuzana BencokovaEster M Hammond
Mar 27, 2009·The Journal of Biological Chemistry·Jeesun Kim, Paul K Y Wong
Dec 8, 2009·The Journal of Biological Chemistry·Naoe TairaKiyotsugu Yoshida
Feb 17, 2010·The International Journal of Biochemistry & Cell Biology·Sybille Mazurek
Oct 20, 2010·Molecular and Cellular Biology·Heather L ArmataHayla K Sluss
Oct 23, 2010·Science·Zhi GuoTanya T Paull
Nov 1, 2011·Nature Medicine·Kristin M NiemanErnst Lengyel
Jan 31, 2012·Cellular Signalling·Paul D RayYoshiaki Tsuji
Feb 15, 2012·The Journal of Experimental Medicine·Robert B Hamanaka, Navdeep S Chandel
Jul 25, 2012·Trends in Endocrinology and Metabolism : TEM·Weibo Luo, Gregg L Semenza
Oct 23, 2012·Cell Cycle·Ubaldo E Martinez-OutschoornMichael P Lisanti
Dec 1, 2012·Biochimica Et Biophysica Acta·Edna Ayerim Mandujano-TinocoSara Rodríguez-Enríquez
Jul 13, 2013·Chinese Journal of Cancer·Christopher P GuiseKe Ding
Sep 4, 2013·The Journal of Clinical Investigation·Joanne R Doherty, John L Cleveland
Feb 4, 2014·Seminars in Cancer Biology·Ubaldo E Martinez-OutschoornFederica Sotgia
Apr 5, 2014·Nature Communications·Paula Lopez-SerraManel Esteller
Apr 22, 2015·Cell·Dong Chul LeeYoung Il Yeom
Jun 16, 2015·The International Journal of Biochemistry & Cell Biology·Sara Rodríguez-EnríquezRafael Moreno-Sánchez
Jun 13, 2017·Trends in Pharmacological Sciences·Guan-Zhong QiuWei-Lin Jin

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Citations

May 23, 2019·Current Opinion in Clinical Nutrition and Metabolic Care·Andrew RedfernErik W Thompson
Aug 6, 2020·Cancer Management and Research·Yanhong HaoZhibin Zhang
Nov 19, 2019·Frontiers in Oncology·Karen G de la Cruz-LópezJoaquín Manzo-Merino
Mar 3, 2021·Metabolic Brain Disease·Harkomal VermaAnil K Mantha
Mar 16, 2021·Critical Reviews in Oncology/hematology·RamaRao MallaGanji Purnachandra Nagaraju
Jul 28, 2020·Biochimica Et Biophysica Acta. General Subjects·Álvaro Marín-HernándezEmma Saavedra
Apr 10, 2021·Frontiers in Cell and Developmental Biology·Thais SobanskiEmma Bolderson
Apr 21, 2021·Cell Cycle·Danilo CucchiSarah A Martin
Jun 11, 2021·Signal Transduction and Targeted Therapy·Fanglong WuHongmei Zhou
Oct 17, 2021·Journal of Hematology & Oncology·Yiyin ZhangHui Lin
Oct 22, 2021·Molecular Cancer Research : MCR·Thomas Simon, Bodour Salhia

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Methods Mentioned

BETA
genotyping
protein assay
Co-immunoprecipitation
Assay
transmission electron microscopy
flow cytometry
xenografts
immunoprecipitation
transfection
pull-down

Software Mentioned

SPSS

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