Journal for ImmunoTherapy of Cancer, 18 June, 2021, DOI：http://dx.doi.org/10.1136/jitc-2021-002548
S100A4 enhances protumor macrophage polarization by control of PPAR-γ-dependent induction of fatty acid oxidation
Shuangqing Liu, Huilei Zhang, Yanan Li, Yana Zhang, Yangyang Bian, Yanqiong Zeng, Xiaohan Yao, Jiajia Wan, Xu Chen, Jianru Li, Zhaoqing Wang and Zhihai Qin
The peroxisome proliferator-activated receptor γ (PPAR-γ)-dependent upregulation of fatty acid oxidation (FAO) mediates protumor (also known as M2-like) polarization of tumor-associated macrophages (TAMs). However, upstream factors determining PPAR-γ upregulation in TAM protumor polarization are not fully identified. S100A4 plays crucial roles in promotion of cancer malignancy and mitochondrial metabolism. The fact that macrophage-derived S100A4 is major source of extracellular S100A4 suggests that macrophages contain a high abundance of intracellular S100A4. However, whether intracellular S100A4 in macrophages also contributes to cancer malignancy by enabling TAMs to acquire M2-like protumor activity remains unknown.