Microcystin-LR Regulates Interaction Between Tumor Cells and Macrophages Via the IRE1α/XBP1 Signaling Pathway to Promote the Progression of Colorectal Cancer

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2024 Sep 14

PMID 39273011

Authors

Xiaochang Wang

Yuechi Song

Xiaohui Lu

Hengshuo Zhang

Ting Wang

Affiliations

Soon will be listed here.

Abstract

Microcystin-LR (MC-LR), a cyanobacterial toxin, is a potent carcinogen implicated in colorectal cancer (CRC) progression. However, its impact on the tumor microenvironment (TME) during CRC development remains poorly understood. This study investigates the interaction between tumor cells and macrophages mediated by MC-LR within the TME and its influence on CRC progression. CRC mice exposed to MC-LR demonstrated a significant transformation from adenoma to adenocarcinoma. The infiltration of macrophages increased, and the IRE1α/XBP1 pathway was activated in CRC cells after MC-LR exposure, influencing macrophage M2 polarization under co-culture conditions. Additionally, hexokinase 2 (HK2), a downstream target of the IRE1α/XBP1 pathway, was identified, regulating glycolysis and lactate production. The MC-LR-induced IRE1α/XBP1/HK2 axis enhanced lactate production in CRC cells, promoting M2 macrophage polarization. Furthermore, co-culturing MC-LR-exposed CRC cells with macrophages, along with the IRE1α/XBP1 pathway inhibitor 4μ8C and the hexokinase inhibitor 2-DG, suppressed M2 macrophage-induced CRC cell migration, clonogenicity, and M2 macrophage polarization. This study elucidates the mechanism by which MC-LR-mediated interactions through the IRE1α/XBP1 pathway promote CRC progression, highlighting potential therapeutic targets.

Citing Articles

Role of cyanotoxins in the development and promotion of cancer.

Rajput S, Jain S, Dash D, Gupta N, Rajpoot R, Upadhyaya C Toxicol Rep. 2024; 13:101798.

PMID: 39606777 PMC: 11600067. DOI: 10.1016/j.toxrep.2024.101798.

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