Macrophage-Associated PGK1 Phosphorylation Promotes Aerobic Glycolysis and Tumorigenesis

Molecular Cell
Yajuan ZhangWeiwei Yang

Abstract

Macrophages are a dominant leukocyte population in the tumor microenvironment and actively promote cancer progression. However, the molecular mechanism underlying the role of macrophages remains poorly understood. Here we show that polarized M2 macrophages enhance 3-phosphoinositide-dependent protein kinase 1 (PDPK1)-mediated phosphoglycerate kinase 1 (PGK1) threonine (T) 243 phosphorylation in tumor cells by secreting interleukin-6 (IL-6). This phosphorylation facilitates a PGK1-catalyzed reaction toward glycolysis by altering substrate affinity. Inhibition of PGK1 T243 phosphorylation or PDPK1 in tumor cells or neutralization of macrophage-derived IL-6 abrogates macrophage-promoted glycolysis, proliferation, and tumorigenesis. In addition, PGK1 T243 phosphorylation correlates with PDPK1 activation, IL-6 expression, and macrophage infiltration in human glioblastoma multiforme (GBM). Moreover, PGK1 T243 phosphorylation also correlates with malignance and prognosis of human GBM. Our findings demonstrate a novel mechanism of macrophage-promoted tumor growth by regulating tumor cell metabolism, implicating the therapeutic potential to disrupt the connection between macrophages and tumor cells by inhibiting PGK1 phosphorylation.

Citations

Apr 2, 2020·International Journal of Molecular Sciences·Guilherme Wesley Peixoto da FonsecaMitja Lainscak
Mar 29, 2020·The Journal of Biological Chemistry·Chengmeng JinXun Hu
Jul 11, 2020·Aging·Jinyu ZhengJian Sun
Aug 21, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chen LiHongchang Gao
Jun 23, 2020·Mediators of Inflammation·Fakai WangZengchao Zhang
Jul 13, 2020·Cellular and Molecular Life Sciences : CMLS·Fang WeiZhaoyang Zeng
Aug 4, 2020·World Journal of Stem Cells·Xuan ZhuZhi-Gang Chen
Nov 27, 2019·Cell Death & Disease·Jinqian LiangMing-Sheng Tan
Jul 1, 2020·F1000Research·Shensi Shen, Jean Clairambault
Feb 10, 2020·Translational Stroke Research·Lizhen FanYun Xu
Jun 5, 2019·Genes & Development·Ryan C GimpleJeremy N Rich
Jul 1, 2020·Frontiers in Cellular and Infection Microbiology·Qing YuGuangwei Liu
Dec 22, 2020·Frontiers in Cell and Developmental Biology·Tianxin YeXuewu Zhang
Jan 3, 2021·Frontiers of Medicine·Lei Lv, Qunying Lei
Nov 12, 2020·Biology·Kyra E de GoedeJan Van den Bossche
Dec 31, 2020·Cells·Alessandra De LeoFilippo Veglia
Oct 24, 2020·Biochemical and Biophysical Research Communications·Zhongwei LiJin Bai
Nov 5, 2020·Archives of Biochemistry and Biophysics·Tao YuXiongbin Lu
Jul 4, 2019·Cell Metabolism·Ilio VitaleLorenzo Galluzzi
Mar 18, 2021·Advanced Biology·Jia XiongQingqing Wang
Nov 7, 2020·Frontiers in Immunology·Thomas DaubonMaya Saleh
Jun 9, 2021·Cancer Cell International·Tiecheng WangWei Yu
Jul 3, 2021·Frontiers in Cell and Developmental Biology·Runze QiuHongwei Fan

❮ Previous
Next ❯

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

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 Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

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.