{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:45:37Z","timestamp":1790718337501,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"R\u00e9gion Franche-Comt\u00e9","award":["LabEx LipSTIC ANR-11-LABX-0021."],"award-info":[{"award-number":["LabEx LipSTIC ANR-11-LABX-0021."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Bladder cancer aggressiveness is correlated with abnormal N-cadherin transmembrane glycoprotein expression. This protein is cleaved by the metalloprotease ADAM10 and the \u03b3-secretase complex releasing a pro-angiogenic N-terminal fragment (NTF) and a proliferation-activating soluble C-terminal fragment (CTF2). Tetraspanin 15 (Tspan15) is identified as an ADAM10-interacting protein to induce selective N-cadherin cleavage. We first demonstrated, in invasive T24 bladder cancer cells, that N-cadherin was cleaved by ADAM10 generating NTF in the extracellular environment and leaving a membrane-anchored CTF1 fragment and that Tspan15 is required for ADAM10 to induce the selective N-cadherin cleavage. Targeting N-cadherin function in cancer is relevant to preventing tumor progression and metastases. For antitumor molecules to inhibit N-cadherin function, they should be complete and not cleaved. We first showed that the GW501516, an agonist of the nuclear receptor PPAR\u03b2\/\u03b4, decreased Tspan15 and prevented N-cadherin cleavage thus decreasing NTF. Interestingly, the drug did not modify ADAM10 expression, which was important because it could limit side effects since ADAM10 cleaves numerous substrates. By targeting Tspan15 to block ADAM10 activity on N-cadherin, GW501516 could prevent NTF pro-tumoral effects and be a promising molecule to treat bladder cancer. More interestingly, it could optimize the effects of the N-cadherin antagonists those such as ADH-1 that target the N-cadherin ectodomain.<\/jats:p>","DOI":"10.3390\/cells13080708","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T06:28:09Z","timestamp":1713508089000},"page":"708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["GW501516-Mediated Targeting of Tetraspanin 15 Regulates ADAM10-Dependent N-Cadherin Cleavage in Invasive Bladder Cancer Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Alexandre","family":"Barbaud","sequence":"first","affiliation":[{"name":"SINERGIES\u2013LabEx LipSTIC ANR-11-LABX-0021, Universit\u00e9 de Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Lascombe","sequence":"additional","affiliation":[{"name":"SINERGIES\u2013LabEx LipSTIC ANR-11-LABX-0021, Universit\u00e9 de Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"P\u00e9chery","sequence":"additional","affiliation":[{"name":"SINERGIES\u2013LabEx LipSTIC ANR-11-LABX-0021, Universit\u00e9 de Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergen","family":"Arslan","sequence":"additional","affiliation":[{"name":"SINERGIES\u2013LabEx LipSTIC ANR-11-LABX-0021, Universit\u00e9 de Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Kleinclauss","sequence":"additional","affiliation":[{"name":"CHU Besan\u00e7on, Service Urologie, Andrologie et Transplantation R\u00e9nale, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Fauconnet","sequence":"additional","affiliation":[{"name":"SINERGIES\u2013LabEx LipSTIC ANR-11-LABX-0021, Universit\u00e9 de Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"},{"name":"CHU Besan\u00e7on, Service Urologie, Andrologie et Transplantation R\u00e9nale, F-25000 Besan\u00e7on, France"},{"name":"CHU Besan\u00e7on, Centre Investigation Clinique, Inserm CIC 1431, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0304-3835(01)00759-5","article-title":"Cadherins and the tumour progression: Is it all in a switch?","volume":"176","author":"Cavallaro","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Noronha, C., Ribeiro, A.S., Taipa, R., Castro, D.S., Reis, J., Faria, C., and Paredes, J. 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