Microcystin-LR Regulates Interaction between Tumor Cells and Macrophages via the IRE1α/XBP1 Signaling Pathway to Promote the Progression of Colorectal Cancer
》》Journal：Cells.
》》相关产品：2-Deoxy-D-glucose (2-DG) (SJ-MN0028) 和 4μ8C (SJ-MX0449)
》》产品引用描述：
》》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.
》》部分文献数据展示：
Figure 7. The combined treatment with 2-DG and 4µ8C suppressed the progression of CRC induced by MC-LR in both individual and co-culture culture conditions. Cell viability of (A) DLD-1 and (B) HCT116 cells was assessed under exposure to inhibitors (2-DG and 4µ8C), MC-LR (10 and 100 nM), and a combination of inhibitors (2-DG and 4µ8C) with MC-LR. 2-DG: 100µM; 4µ8C: 100nM. Relative expression levels of M2 markers (CD206, ARG1, PPARγ) in M0 macrophages co-cultured with (C) DLD-1 and (D) HCT116 cells, respectively, after 48 h exposure to MC-LR alone or in combination with inhibitors (2-DG and 4µ8C).
