Qianying Kong1, Yancan Liang2, Qifen He3, Yingying You3, Lifen Wu3, Lizhong Liang3, Jun Liang3. 1. Zhuhai Stomatology Hospital, Zhuhai, Guangdong, China. 2. Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. 3. Department of Oral and Maxillofacial Surgery, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.
Abstract
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.
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.
Authors: Daniel Peña-Oyarzún; Montserrat Reyes; María Paz Hernández-Cáceres; Catalina Kretschmar; Eugenia Morselli; Cesar A Ramirez-Sarmiento; Sergio Lavandero; Vicente A Torres; Alfredo Criollo Journal: Front Oncol Date: 2020-12-09 Impact factor: 6.244
Authors: Fernanda Visioli; Julia Silveira Nunes; Maria Carmela Pedicillo; Rosalia Leonardi; Angela Santoro; Gian Franco Zannoni; Gabriella Aquino; Margherita Cerrone; Monica Cantile; Nunzia Simona Losito; Vito Rodolico; Giuseppina Campisi; Giuseppe Colella; Ilenia Sara De Stefano; Maria Antonietta Ramunno; Cristina Pizzulli; Marco Visconti; Lorenzo Lo Muzio; Giuseppe Pannone Journal: Biomolecules Date: 2022-02-28