Autophagy inhibits TLR4‐mediated invasiveness of oral cancer cells via the NF‐κB pathway

• Published in: Oral diseases Vol. 26; no. 6; pp. 1165 - 1174
• Main Authors: Kong, Qianying, Liang, Yancan, He, Qifen, You, Yingying, Wu, Lifen, Liang, Lizhong, Liang, Jun
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.09.2020
• Subjects: Autophagy; Cervix; Cytoplasm; invasion; Invasiveness; Lipopolysaccharides; Metastases; NF‐κB pathway; Oral cancer; oral squamous cell carcinoma; Phagocytosis; Signal transduction; Squamous cell carcinoma; TLR4; TLR4 protein; Toll-like receptors; Oral Squamous Cell Carcinoma; Autophagy; TLR4; Invasion; NF-κB Pathway
• ISSN: 1354-523X; 1601-0825; 1601-0825
• DOI: 10.1111/odi.13355

Objectives Toll‐like receptor 4 (TLR4) is abnormally expressed in oral cancer tissues and promotes cancer cell invasion. The purpose of this study was to clarify the mechanism by which autophagy regulates oral cancer invasion through the TLR4‐NF‐κB pathway. Subjects and Methods We examined TLR4 expression in oral cancer tissues and analysed the relationship between its expression and clinicopathological features. The invasion and migration of LPS‐stimulated oral cancer cells with up‐ or downregulation of TLR4 expression was detected in addition to NF‐κB signalling and autophagy levels. Furthermore, the role of autophagy in regulating TLR4‐mediated cell invasiveness was explored by silencing the expression of key autophagy genes ATG7 and p62. Results We found that TLR4 overexpression was closely related to cervical lymphatic metastasis and poor survival. TLR4 activated the NF‐κB pathway to promote the invasiveness of OSCC cells, and autophagy partly inhibited invasiveness by suppressing the NF‐κB pathway. We observed that p62 translocated from the cytoplasm to the nucleus when autophagy was activated by LPS. Finally, silencing p62 further promoted LPS‐mediated cell invasiveness. Conclusion Toll‐like receptor 4 significantly enhanced the invasiveness of OSCC cells. Autophagy may regulate cell invasiveness through the NF‐κB pathway by modulating both the cytoplasmic and nuclear levels of p62.