Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/STAT3 signaling pathway in breast cancer

Cell Cycle
Xianmin MuQiang You

Abstract

Tumor-associated macrophages (TAM) are prominent components of tumor microenvironment (TME) and capable of promoting cancer progression. However, the mechanisms for the formation of M2-like TAMs remain enigmatic. Here, we show that lactate is a pivotal oncometabolite in the TME that drives macrophage M2-polarization to promote breast cancer proliferation, migration, and angiogenesis. In addition, we identified that the activation of ERK/STAT3, major signaling molecules in the lactate signaling pathway, deepens our molecular understanding of how lactate educates TAMs. Moreover, suppression of ERK/STAT3 signaling diminished tumor growth and angiogenesis by abolishing lactate-induced M2 macrophage polarization. Finally, research data of the natural compound withanolide D provide evidence for ERK/STAT3 signaling as a potential therapeutic strategy for the prevention and treatment of breast cancer. These findings suggest that the lactate-ERK/STAT3 signaling pathway is a driver of breast cancer progression by stimulating macrophage M2-like polarization and reveal potential new therapeutic targets for breast cancer treatment.

References

Mar 10, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Fayaz MalikJaswant Singh
Jul 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Weijuan ZhangSidong Xiong
Oct 26, 2011·Nature Reviews. Immunology·Toby Lawrence, Gioacchino Natoli
Jun 7, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xianmin MuLuyong Zhang
Mar 29, 2014·F1000prime Reports·Fernando O Martinez, Siamon Gordon
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Jul 25, 2015·Metabolomics : Official Journal of the Metabolomic Society·B VaitheesvaranW N Lee
Feb 26, 2016·Frontiers in Immunology·Susana Romero-GarciaFrancisco Javier Sánchez-García
Aug 9, 2016·Phytochemistry·Pedro Henrique J BatistaOtília Deusdenia L Pessoa
Jan 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Peiwen ChenYihong Wan
Apr 11, 2017·Current Medicinal Chemistry·Stefania SutStefano Dall Acqua
Jun 21, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna E BoniakowskiKatherine A Gallagher
Jun 27, 2017·The Journal of Clinical Investigation·Karishma RahmanEdward A Fisher
Jul 12, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Haruka ShinoharaYukihiro Akao
Aug 28, 2017·Drug Discovery Today·Rakesh K Tekade, Xiankai Sun
Sep 9, 2017·Oncotarget·Ting ZhaoQiang You
Oct 5, 2017·Nature Communications·Zhiyuan NiuPingping Shen
Oct 7, 2017·Cell·Brandon FaubertRalph J DeBerardinis

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Citations

Mar 15, 2019·Clinical and Experimental Immunology·J Lötscher, M L Balmer
Jun 23, 2019·Cells·Takahiko Murayama, Noriko Gotoh
Feb 1, 2019·Processes·Kerri-Ann NortonAleksander S Popel
Dec 17, 2019·Antioxidants & Redox Signaling·Jia Yu LeungReshma Taneja
Nov 7, 2019·Apoptosis : an International Journal on Programmed Cell Death·Yun-Ji LimChang-Hwa Song
Mar 21, 2020·Endocrinology·Juan H Vasquez, Jeremy C Borniger
May 12, 2020·Oncotarget·Alexander K VermaW Keith Miskimins
Jan 30, 2020·International Journal of Cancer. Journal International Du Cancer·Alaa Madi, Guoliang Cui
Dec 8, 2019·Virchows Archiv : an International Journal of Pathology·Melissa AlameVanessa Szablewski
Aug 23, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Cindy Mendes, Jacinta Serpa
Jul 6, 2018·Cancer Immunology, Immunotherapy : CII·Ruben LacroixChristian U Blank
May 14, 2019·The Journal of Clinical Investigation·Benjamin D Singer, Navdeep S Chandel
Jul 1, 2018·International Journal of Particle Therapy·Mathieu SertorioSusanne I Wells
Mar 18, 2020·Frontiers in Immunology·Li-Na MaAi-Hua Liao
Oct 1, 2020·International Journal of Molecular Sciences·Bilash ChatterjeeAmit Kumar Srivastava
Aug 9, 2020·Frontiers in Cell and Developmental Biology·Xiangyu SunYingying Xu
Jul 22, 2019·Cancers·So-Yeon ParkJeong-Seok Nam
May 24, 2019·International Journal of Molecular Sciences·Iris C SalaroglioChiara Riganti
Jan 8, 2020·International Journal of Molecular Sciences·Louise InjarabianBenoit S Marteyn
Apr 17, 2020·Frontiers in Oncology·Xiangyu SunYingying Xu
Nov 19, 2019·Frontiers in Oncology·Karen G de la Cruz-LópezJoaquín Manzo-Merino
Oct 14, 2020·Journal of Biochemical and Molecular Toxicology·Sara MorsyWafaa M Ibrahim
Oct 27, 2020·Cancer Immunology, Immunotherapy : CII·Xin PangYa-Ling Tang
Oct 30, 2020·International Journal of Molecular Sciences·Jan KorbeckiPiotr Dzięgiel
Jun 12, 2020·Cancer Letters·Rui HuJian Zhang
Dec 10, 2019·Trends in Cancer·Kamiya Mehla, Pankaj K Singh
Jan 9, 2021·Frontiers in Oncology·Anna Mukha, Anna Dubrovska

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Methods Mentioned

BETA
PCR
xenograft

Software Mentioned

Pro Plus
Image

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