{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T07:10:32Z","timestamp":1789197032953,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T00:00:00Z","timestamp":1471824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Carroll Feist pre-doctoral fellowship","award":["148741195A"],"award-info":[{"award-number":["148741195A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>Tumor cell invasion through the extracellular matrix is facilitated by the secretion of lysosome\u2010associated 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\u2010invasive 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\u2010driven 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\u2010dimensional (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\u2010ribosylation like protein 8b (Arl8b) reversed the invasive phenotype of mesenchymal cells, thus supporting a role for lysosome positioning in EMT\u2010mediated 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\u2010driven cancer progression. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.22528","type":"journal-article","created":{"date-parts":[[2016,7,19]],"date-time":"2016-07-19T18:42:59Z","timestamp":1468953779000},"page":"722-734","source":"Crossref","is-referenced-by-count":18,"title":["Zinc finger E\u2010box binding homeobox\u20101 (Zeb1) drives anterograde lysosome trafficking and tumor cell invasion via upregulation of Na+\/H+ Exchanger\u20101 (NHE1)"],"prefix":"10.1002","volume":"56","author":[{"given":"Samantha S.","family":"Dykes","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Louisiana State University Health Science Center \u2212 Shreveport Shreveport Louisiana"},{"name":"Feist Weiller Cancer Center Louisiana State 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