2. Academic Validation
  3. FABP4 in macrophages facilitates obesity-associated pancreatic cancer progression via the NLRP3/IL-1β axis

FABP4 in macrophages facilitates obesity-associated pancreatic cancer progression via the NLRP3/IL-1β axis

  • Cancer Lett. 2023 Sep 21;216403. doi: 10.1016/j.canlet.2023.216403.
Jian Yang 1,  Shujie Liu 1,  Yongzheng Li 1,  Zhiyao Fan 1,  Yufan Meng 1,  Bin Zhou 2,  Guangyong Zhang 3,  Hanxiang Zhan 4
Affiliations

Affiliations

  • 1 Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
  • 2 Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • 3 Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong Province, China. Electronic address: [email protected].
  • 4 Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, China. Electronic address: [email protected].
PMID: 37741433 DOI: 10.1016/j.canlet.2023.216403
Abstract

Obesity is an essential risk factor for pancreatic Cancer (PC). Macrophage-induced inflammation plays a pivotal role in obesity-associated carcinogenesis and disease progression; however, the underlying molecular mechanisms remain unclear. In this study, we found that fatty acid-binding protein 4 (FABP4) overexpressed in serum of obese patients and was associated with poor overall survival. In vivo and in vitro experiments have revealed that FABP4 induces macrophage-related inflammation to promote Cancer cell migration, invasion and metastasis under obese condition. Mechanistically, FABP4 participates in transferring saturated fatty acid to induce macrophages Pyroptosis in a Caspase-1/GSDMD-dependent manner and mediates NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/IL-1β axis in macrophages, which further regulates epithelial-mesenchymal transition signals to promote the migration, invasion, and metastasis of PC cells. Our results suggest that FABP4 in macrophages is a crucial regulator of the NLRP3/IL-1β axis to promote the progression of PC under obese conditions, which could act as a promising molecular target for treating of PC patients with obesity.

Keywords

FABP4; Inflammation; Macrophage; Obesity; Pancreatic cancer; Pyroptosis.

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