Tumor associated macrophages (TAMs), one of the most common cell components in tumor microenvironment, have been reported as a key contributor to cancer-related inflammation and enhanced metastatic progression of tumors. To explore the underlying mechanism of TAMs induced tumor progression, tumor associated macrophages were isolated from colorectal cancer patients, and the functional interaction with colorectal cancer cells was analyzed. Our study found that co-culture of TAMs contributed to a glycolytic state in colorectal cancer, which promoted the stem-like phenotypes and cells invasion of tumor cells. In mechanism, TAMs produced the cytokine TGF-β to support HIF1α expression, thereby up-regulating Tribbles Pseudokinase 3 (TRIB3) in tumor cells. Elevated expression of TRIB3 resulted in the activation of β-catenin/Wnt signaling pathway, that eventually enhanced the stem-like phenotypes and cells invasion in colorectal cancer. Our findings provided evidence that TAMs promoted colorectal progression through a HIF1α/TRIB3 dependent manner, and blockade of HIF1α signals efficiently improved the outcome of chemotherapy, describing an innovative approach for colorectal cancer treatment.
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