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USP24 Induces IL‐6 in Tumor‐associated Microenvironment through stabilizing p300 and β‐TrCP to Promote the Malignancy of Lung Cancer
Author(s) -
HUNG JanJong
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.654.1
Subject(s) - lung cancer , metastasis , gene knockdown , cancer research , angiogenesis , cancer , tumor microenvironment , cancer cell , macrophage , umbilical vein , downregulation and upregulation , medicine , lung , chemistry , immunology , biology , pathology , cell culture , in vitro , biochemistry , gene , genetics
Our previous study indicated that increase in USP24 level in lung cancer facilitates lung cancer metastasis. Our recent study found that higher USP24 level was found in tumor‐associated microenvironment (TAM) than surrounding lung cancer cells in lung cancer patient specimens. USP24 level was significantly increased in M2‐macrophages. Knockdown of USP24 in M2‐macrophages decreased the migratory and chemotactic activity of lung cancer cells and angiogenetic ability of human umbilical vein endothelial cells (HUVEC) induced by M2‐derived conditioned medium. In vivo experiments also showed USP24 knockdown decreased M2‐macrophages induced lung cancer cells metastasis and angiogenesis. IL‐6 mRNA and protein levels were significantly decreased in USP24 knockdown M2‐macrophages and lung cancer cells. IL‐6 replenishment can rescue migratory and chemotactic ability of conditioned medium derived from USP24 knockdown M2‐macrophages, suggesting that increase in USP24 in M2‐macrophages induce the metastasis activity of lung through promoting IL‐6 expression. To address the molecular mechanism of how USP24 regulated IL‐6 in M2‐macrophage and lung cancer cells, we found that USP24 stabilized p300, thereby increased the transcriptional activity of IL‐6. USP24 could also decreased DNM1 and IkB level through stabilizing β‐TrCP and resulted in upregulated IL‐6. Metastatic cytokines in tumor‐associated microenvironment are important for cancer progression, in this study, we provide the direct evidence to support that USP24 increased in M2‐macrophages and lung cancer cells positive regulates the metastasis of lung cancer through enhancing the IL‐6 expression, which might be beneficial for the drug development for cancer therapy in the future. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .