TRAF6 regulates the signaling pathway influencing colorectal cancer function through ubiquitination mechanisms.

Abstract

Tumor necrosis factor receptor-associated factor-6 (TRAF6) is a ubiquitin E3 ligase. TRAF6 plays an important role in tumor invasion and metastasis. However, the specific mechanism by which TRAF6 promotes colorectal cancer (CRC) metastasis is incompletely understood. This study aimed to determine whether TRAF6 affects the LPS-NF-κB-VEGF-C signaling pathway through ubiquitination, which plays a role in colorectal cancer metastasis. Here, our results showed that TRAF6 affected lymphangiogenesis through the LPS-NF-κB-VEGF-C signaling pathway. Using ubiquitination experiments, we found that TRAF6 was mainly ubiquitinated with the K63-linked chains, and LPS promoted ubiquitination of TRAF6 and K63-linked chains. More importantly, TRAF6 124mut is the main ubiquitination site of TRAF6 interacting with K63-linked chains. TRAF6 affected the migration, invasion, and lymphatic metastasis of colorectal cancer through its ubiquitination. In subcutaneous xenograft models, TRAF6 124mut inhibited tumor growth. In conclusion, our results provide new insight for studying the mechanism of lymphangiogenesis in colorectal cancer to promote cancer metastasis, which may provide new ideas for tumor immunotherapy.

• Authors: Zhu Guangwei, Cheng Zhibin, Wang Qin, Lin Chunlin, Lin Penghang, He Ruofan, Chen Hui, Robert M Hoffman, Ye Jianxin
• Journal: Cancer science (Cancer Sci) Vol. 113 Issue 4 Pg. 1393-1405 (Apr 2022) ISSN: 1349-7006 [Electronic] England
• PMID: 35179811 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Intracellular Signaling Peptides and Proteins
• Lipopolysaccharides
• NF-kappa B
• TNF Receptor-Associated Factor 6
• Tifab protein, human
• Ubiquitin
• Vascular Endothelial Growth Factor C

Topics

• Colorectal Neoplasms (pathology)
• Humans
• Intracellular Signaling Peptides and Proteins
• Lipopolysaccharides (metabolism)
• NF-kappa B (metabolism)
• Signal Transduction
• TNF Receptor-Associated Factor 6 (genetics, metabolism)
• Ubiquitin (metabolism)
• Ubiquitination
• Vascular Endothelial Growth Factor C (metabolism)