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000182766 037__ $$aDKFZ-2022-02906
000182766 041__ $$aEnglish
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000182766 1001_ $$00000-0003-2435-9061$$aTang, Wing Chung$$b0
000182766 245__ $$aLatent Membrane Protein 1 and macrophage-derived TNFα synergistically activate and mobilize invadopodia to drive invasion of nasopharyngeal carcinoma.
000182766 260__ $$aBognor Regis [u.a.]$$bWiley$$c2023
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000182766 500__ $$a2023 Feb;259(2):163-179
000182766 520__ $$aInvadopodia are actin-rich membrane protrusions that digest the matrix barrier during cancer metastasis. Since the discovery of invadopodia, they were visualized as localized and dot-like structures in different types of cancer cells on top of a 2D matrix. In this investigation of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), a highly invasive cancer frequently accompanied by neck lymph node and distal organ metastases, we revealed a new form of invadopodium with mobilizing features. Integration of live-cell imaging and molecular assays revealed the interaction of macrophage-released TNFα and EBV-encoded latent membrane protein 1 (LMP1) in co-activating the EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for mobilizing the invadopodia with lateral movements. This phenomenon endows the invadopodia with massive degradative power, visualized as a shift of focal dot-like digestion patterns on a 2D gelatin to a dendrite-like digestion pattern. Notably, single stimulation of either LMP1 or TNFα could only enhance the number of ordinary dot-like invadopodia, suggesting that the EBV infection sensitizes the NPC cells to form mobilizing invadopodia when encountering a TNFα-rich tumor microenvironment. This study unveils the interplay of EBV and stromal components in driving the invasive potential of NPC via unleashing the propulsion of invadopodia in overcoming matrix hurdles. This article is protected by copyright. All rights reserved.
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000182766 650_7 $$2Other$$aEpstein-Barr virus infection
000182766 650_7 $$2Other$$ainvadopodia
000182766 650_7 $$2Other$$ainvasion
000182766 650_7 $$2Other$$alatent membrane protein 1
000182766 650_7 $$2Other$$alive-cell imaging
000182766 650_7 $$2Other$$anasopharyngeal carcinoma
000182766 650_7 $$2Other$$atumor-associated macrophage
000182766 7001_ $$aTsao, Sai Wah$$b1
000182766 7001_ $$aJones, Gareth E$$b2
000182766 7001_ $$aLiu, Xiong$$b3
000182766 7001_ $$aTsai, Ming Han$$b4
000182766 7001_ $$0P:(DE-He78)25d3c74b949988c637571e696fc04b25$$aDelecluse, Henri-Jacques$$b5$$udkfz
000182766 7001_ $$00000-0002-5558-0685$$aDai, Wei$$b6
000182766 7001_ $$aYou, Chanping$$b7
000182766 7001_ $$aZhang, Jun$$b8
000182766 7001_ $$aHuang, Shaina Chor Mei$$b9
000182766 7001_ $$aLeung, Manton Man-Hon$$b10
000182766 7001_ $$aLiu, Tengfei$$b11
000182766 7001_ $$aChing, Yick Pang$$b12
000182766 7001_ $$aChen, Honglin$$b13
000182766 7001_ $$00000-0002-3488-6124$$aLo, Kwok Wai$$b14
000182766 7001_ $$aLi, Xin$$b15
000182766 7001_ $$aTsang, Chi Man$$b16
000182766 773__ $$0PERI:(DE-600)1475280-3$$a10.1002/path.6036$$gp. path.6036$$n2$$p163-179$$tThe journal of pathology$$v259$$x0022-3417$$y2023
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