{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:18Z","timestamp":1787028558316,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Namur (Namur, Belgium)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mutations in GNPTAB underlie mucolipidosis II and mucolipidosis III \u03b1\/\u03b2, which are inherited lysosomal storage disorders caused by a defective UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine phosphotransferase. As a result, newly synthesized acid hydrolases fail to acquire Mannose-6-Phosphate (Man-6-P) sorting signals, or do so to a lesser extent, and exhibit an impaired trafficking to lysosomes. Interestingly, we found that GNPTAB knockout HeLa cells are resistant to several cytotoxic agents: doxorubicin, chloroquine, staurosporine and paclitaxel. While we detected an increased trapping of weak bases in the expanded lysosomal population of these cells, which could reduce the effect of doxorubicin and chloroquine; the decreased cell response to staurosporine and paclitaxel suggested the involvement of alternative resistance mechanisms. Indeed, further investigation revealed that the hyperactivation of the Insulin-like Growth Factor 1 Receptor (IGF1R) pathway is a central player in the apoptosis resistance exhibited by Man-6-P sorting deficient cells.<\/jats:p>","DOI":"10.3390\/ijms26083586","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T11:26:41Z","timestamp":1744284401000},"page":"3586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disruption of Man-6-P-Dependent Sorting to Lysosomes Confers IGF1R-Mediated Apoptosis Resistance"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3669-8888","authenticated-orcid":false,"given":"Asena","family":"Aynaci","sequence":"first","affiliation":[{"name":"Laboratory of Intracellular Trafficking Biology, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"},{"name":"Laboratory of Physiological Chemistry, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxence","family":"Toussaint","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Trafficking Biology, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"},{"name":"Laboratory of Physiological Chemistry, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florentine","family":"Gilis","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Trafficking Biology, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"},{"name":"Laboratory of Physiological Chemistry, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Albert","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Trafficking Biology, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Gaussin","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Trafficking Biology, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7425-3006","authenticated-orcid":false,"given":"Michel","family":"Jadot","sequence":"additional","affiliation":[{"name":"Laboratory of Physiological Chemistry, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Boonen","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Trafficking Biology, URPhyM, NARILIS, UNamur, 61 rue de Bruxelles, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1096\/fasebj.1.6.3315809","article-title":"Trafficking of lysosomal enzymes","volume":"1","author":"Kornfeld","year":"1987","journal-title":"Faseb J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.bi.55.070186.001123","article-title":"Lysosomal enzymes and their receptors","volume":"55","author":"Hasilik","year":"1986","journal-title":"Annu. 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