Qi Yi-Jun, Jiao Ye-Lin, Chen Pan, Zhu Qiao-Qing, Guo Ran, Wu Dang-Rou, Du Yu-Bo, Li Wan-Ying, Cheng Yue-Yue, Wu Xiao-Shuang, Li Meng-Xiang, Li Wei, Gao Shegan
State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang 471003, China.
Department of Pathology, The First People's Hospital of Luoyang, Luoyang 471002, China.
Cell Signal. 2025 Nov;135:111974. doi: 10.1016/j.cellsig.2025.111974. Epub 2025 Jul 5.
Porphyromonas gingivalis (P. gingivalis), a keystone pathogen in adult periodontitis, is linked to an increased risk of many cancers. Although autophagy stimulated by P. gingivalis in ESCC has been reported, the molecular mechanisms and functional roles of autophagy in P. gingivalis-related ESCC progression are still unclear. P. gingivalis infection promoted the malignant progression of ESCC through autophagy, as demonstrated in both in vitro and in vivo studies. Once P. gingivalis invaded cancer cells, it induced the dephosphorylation and nuclear accumulation of YAP/TAZ, which are the effectors of Hippo pathway. In a TEAD-dependent manner, YAP/TAZ activated the miR-21-5p/RASA1/ERK signaling pathway to enhance autophagy-mediated tumor-promoting roles in the proliferation, migration, and invasion of ESCC. Additionally, P. gingivalis infection was correlated with higher levels of miR-21-5p, YAP/TAZ, and LC3, all of which were associated with shorter overall survival of patients with ESCC. Taken together, our findings reveal that the YAP/TAZ-miR-21-5p-ERK axis plays a crucial role in the P. gingivalis-infected subtype of ESCC, suggesting P. gingivalis and the autophagy pathway as promising therapeutic targets for ESCC treatment.
