Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression.

Metabolic reprogramming greatly contributes to the regulation of macrophage activation. However, the mechanism of lipid accumulation and the corresponding function in tumor-associated macrophages (TAMs) remain unclear. With primary investigation in colon cancer and confirmation in other cancer models, here we determine that deficiency of monoacylglycerol lipase (MGLL) results in lipid overload in TAMs.

NF-κB potentiates tumor growth by suppressing a novel target LPTS.

Background: Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incompletely elucidated.

Macrophages induce resistance to 5-fluorouracil chemotherapy in colorectal cancer through the release of putrescine.

The development of chemoresistance to 5-fluorouracil (5-FU) is a major obstacle for sustained effective treatment of colorectal cancer (CRC), with the mechanisms being not fully understood. Here we demonstrated that tumor associated macrophages (TAMs) became activated during treatment with 5-FU and secreted factors that protected the CRC cells against chemotherapy with 5-FU. By performing metabolomics analysis, we identified putrescine, a member of polyamines, inducing resistance to 5-FU-triggered CRC apoptosis and tumor suppression via JNK-caspase-3 pathway.

Macrophage TCF-4 co-activates p65 to potentiate chronic inflammation and insulin resistance in mice.

Transcription factor 4 (TCF-4) was recently identified as a candidate gene for the cause of type 2 diabetes, although the mechanisms have not been fully elucidated. In the present study, we demonstrated that the TCF-4 transgene in macrophages aggravated high-fat diet (HFD)-induced insulin resistance and chronic inflammation, characterized by the elevation of proinflammatory cytokines in the blood, liver and white adipose tissue, as well as a proinflammatory profile of immune cells in visceral fats in mice. Mechanistically, TCF-4 functioned as a co-activator of p65 to amplify the saturated free fatty acid (FFA)-stimulated promoter activity, mRNA transcription and secretion of proinflammatory cytokines in primary macrophages.