Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 702, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2021.108838
Keywords
Gastric cancer; YAP1; IL13; Tumor associated macrophage; Glycometabolism reprogramming; 5-FU
Categories
Funding
- Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer [2020B121201004]
- Guangzhou Science and Technology Project [2019A1515010641]
- Presidential Foundation of Nanfang Hospital, Southern Medical University [2018B002, 2018C030]
- China Postdoctoral Science Foundation [2019M652973]
- National Natural Science Foundation of China [82003289]
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The overexpression of YAP1 in gastric cancer tissues leads to polarization of macrophages into M2-like phenotype, enhancing resistance of tumor cells to 5-FU.
The antimetabolite 5-fluorouracil (5-FU) is a widely used chemotherapy regimen for the treatment of gastric cancer (GC). However, resistance to 5-FU remains a major drawback in the clinical use. The treatments of anti-tumor chemo-agents recruit tumor associated macrophages (TAMs) which are highly implicated in the chemoresistance development, but the underlying molecular mechanism is unclear. Here, we demonstrate that YAP1 is overexpressed in resistant GC tissues compared to sensitive GC tissues. Further, IL-3 secreted by YAP1-overexpressed GC could skew macrophage polarization to M2-like phenotype and inducing GLUT3-depended glycolysis program. Meanwhile, polarized M2 macrophages enhance 5-FU resistance in tumor cells by secreting CCL8 and activating phosphorylation of JAK1/STAT3 signaling pathway.
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