Latent membrane protein 1 and macrophage-derived TNFα synergistically activate and mobilize invadopodia to drive invasion of nasopharyngeal carcinoma.

Autor: Tang WC; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., Tsao SW; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., Jones GE; Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK., Liu X; Department of Otolaryngology - Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, PR China., Tsai MH; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan., Delecluse HJ; Unit F100, DKFZ, Heidelberg, Germany.; Inserm Unit U1074, DKFZ, Heidelberg, Germany., Dai W; Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., You C; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., Zhang J; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China.; Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, Shenzhen University, School of Medicine, Shenzhen, PR China., Huang SCM; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., Leung MM; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., Liu T; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., Ching YP; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., Chen H; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China., Lo KW; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong SAR, PR China., Li X; Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, PR China., Tsang CM; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2023 Feb; Vol. 259 (2), pp. 163-179. Date of Electronic Publication: 2023 Jan 06.
DOI: 10.1002/path.6036
Abstrakt: Invadopodia are actin-rich membrane protrusions that digest the matrix barrier during cancer metastasis. Since the discovery of invadopodia, they have been visualized as localized and dot-like structures in different types of cancer cells on top of a 2D matrix. In this investigation of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), a highly invasive cancer frequently accompanied by neck lymph node and distal organ metastases, we revealed a new form of invadopodium with mobilizing features. Integration of live-cell imaging and molecular assays revealed the interaction of macrophage-released TNFα and EBV-encoded latent membrane protein 1 (LMP1) in co-activating the EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for mobilizing the invadopodia with lateral movements. This phenomenon endows the invadopodia with massive degradative power, visualized as a shift of focal dot-like digestion patterns on a 2D gelatin to a dendrite-like digestion pattern. Notably, single stimulation of either LMP1 or TNFα could only enhance the number of ordinary dot-like invadopodia, suggesting that the EBV infection sensitizes the NPC cells to form mobilizing invadopodia when encountering a TNFα-rich tumor microenvironment. This study unveils the interplay of EBV and stromal components in driving the invasive potential of NPC via unleashing the propulsion of invadopodia in overcoming matrix hurdles. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
(© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
Databáze: MEDLINE
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