2. Academic Validation
  3. Fas signaling in adipocytes promotes low-grade inflammation and lung metastasis of colorectal cancer through interaction with Bmx

Fas signaling in adipocytes promotes low-grade inflammation and lung metastasis of colorectal cancer through interaction with Bmx

  • Cancer Lett. 2021 Dec 1;522:93-104. doi: 10.1016/j.canlet.2021.09.024.
Fei Yang 1,  Meng Duan 1,  Faxiang Zheng 1,  Lei Yu 2,  Yuan Wang 1,  Guowei Wang 1,  Jie Lin 1,  Shuang Han 3,  Da Gan 1,  Zhuoxian Meng 4,  Shankuan Zhu 5
Affiliations

Affiliations

  • 1 Chronic Disease Research Institute, The Children's Hospital, and National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Nutrition and Food Hygiene, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
  • 2 Laboratory of Cancer Biology, The Key Lab of Biotherapy in Zhejiang Sir Run, Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
  • 3 Chronic Disease Research Institute, The Children's Hospital, and National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 4 Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: zxmeng@zju.edu.cn.
  • 5 Chronic Disease Research Institute, The Children's Hospital, and National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Nutrition and Food Hygiene, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: zsk@zju.edu.cn.
PMID: 34536556 DOI: 10.1016/j.canlet.2021.09.024
Abstract

Obesity is a global public health issue. Obesity-related chronic low-grade inflammation (meta-inflammation) can lead to aberrant adipokine release and promote cardiometabolic diseases and obesity-related tumors. However, the mechanisms involved in the initiation of inflammatory responses in obesity and obesity-related tumors as well as metastasis are not fully understood. In this study, we found that the increased tumor necrosis factor-alpha (TNF-α) in adipocytes promoted the lung metastasis of MC38 colon Cancer cells via Fas signaling. The release of TNF-α and interleukin (IL)-6 by Fas signaling in adipocytes was caused by the activation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways mediated by the interaction of Fas with Bmx, a non-receptor tyrosine kinase. Moreover, the Fas/Bmx complex is involved in the inflammation of adipocytes via Fas at the Tyr189 site and SH2 domain of Bmx. This is the first study to report the interaction between Fas and Bmx in adipocyte inflammation, which may provide clues for the development of potential new treatment strategies for obesity-related diseases.

Keywords

Adipocyte; Bmx; Fas signaling; Inflammation; Lung metastasis of colorectal cancer.

Figures
Products