Zinc finger E-box binding homeobox-1 (Zeb1) drives anterograde lysosome trafficking and tumor cell invasion via upregulation of Na+/H+ Exchanger-1 (NHE1).
Zinc finger E-box binding homeobox-1 (Zeb1) drives anterograde lysosome trafficking and tumor cell invasion via upregulation of Na+/H+ Exchanger-1 (NHE1).
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DOI：
10.1002/mc.22528
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发表时间：
2017-03
影响因子：
4.6
通讯作者：
Cardelli JA
中科院分区：
文献类型：
--
作者：
Dykes SS;Gao C;Songock WK;Bigelow RL;Woude GV;Bodily JM;Cardelli JA
Tumor cell invasion through the extracellular matrix is facilitated by the secretion of lysosome-associated proteases. As a common mechanism for secretion, lysosomes must first traffic to the cell periphery (anterograde trafficking), consistent with invasive cells often containing lysosomes closer to the plasma membrane compared to non-invasive cells. Epithelial to mesenchymal transition (EMT) is a transcriptionally-driven program that promotes an invasive phenotype, and Zeb1 is one transcription factor that activates the mesenchymal gene expression program. The role of lysosome trafficking in EMT-driven invasion has not been previously investigated. We found that cells with increased levels of Zeb1 displayed lysosomes located closer to the cell periphery and demonstrated increased protease secretion and invasion in 3-dimensional (3D) cultures compared to their epithelial counterparts. Additionally, preventing anterograde lysosome trafficking via pharmacological inhibition of Na+/H+ exchanger 1 (NHE1) or shRNA depletion of ADP-Ribosylation like protein 8b (Arl8b) reversed the invasive phenotype of mesenchymal cells, thus supporting a role for lysosome positioning in EMT-mediated tumor cell invasion. Immunoblot revealed that expression of Na+/H+ exchanger 1 correlated with Zeb1 expression. Furthermore, we found that the transcription factor Zeb1 binds to the Na+/H+ exchanger 1 promoter, suggesting that Zeb1 directly controls Na+/H+ transcription. Collectively, these results provide insight into a novel mechanism regulating Na+/H+ exchanger 1 expression and support a role for anterograde lysosome trafficking in Zeb1-driven cancer progression.
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DOI：
10.1083/jcb.201103045
发表时间：
2011-11-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Magalhaes MA;Larson DR;Mader CC;Bravo-Cordero JJ;Gil-Henn H;Oser M;Chen X;Koleske AJ;Condeelis J
通讯作者：
Condeelis J
DOI：
10.1038/nrm3141
发表时间：
2011-06-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.5
作者：
Lee, Mei-Yi;Chou, Cheng-Yang;Shen, Meng-Ru
通讯作者：
Shen, Meng-Ru
影响因子：
32.4
作者：
Garg S;Sharma M;Ung C;Tuli A;Barral DC;Hava DL;Veerapen N;Besra GS;Hacohen N;Brenner MB
通讯作者：
Brenner MB
影响因子：
3.3
作者：
Drake, Justin M.;Strohbehn, Garth;Henry, Michael D.
通讯作者：
Henry, Michael D.