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

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.

• Authors: Fei Yang, Meng Duan, Faxiang Zheng, Lei Yu, Yuan Wang, Guowei Wang, Jie Lin, Shuang Han, Da Gan, Zhuoxian Meng, Shankuan Zhu
• Journal: Cancer letters (Cancer Lett) Vol. 522 Pg. 93-104 (12 01 2021) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 34536556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Fas protein, mouse
• Interleukin-6
• NF-kappa B
• Tumor Necrosis Factor-alpha
• fas Receptor
• Bmx protein, mouse
• Protein-Tyrosine Kinases
• Mitogen-Activated Protein Kinase Kinases

Topics

• Adipocytes (metabolism, pathology)
• Animals
• Cell Line, Tumor
• Colorectal Neoplasms (complications, genetics, pathology)
• Disease Models, Animal
• Humans
• Inflammation (genetics, pathology)
• Interleukin-6 (genetics)
• Lung Neoplasms (genetics, secondary)
• Mitogen-Activated Protein Kinase Kinases (genetics)
• NF-kappa B (genetics)
• Neoplasm Metastasis
• Obesity (complications, genetics, pathology)
• Protein-Tyrosine Kinases (genetics)
• Tumor Necrosis Factor-alpha (genetics)
• fas Receptor (genetics)