{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:56:15Z","timestamp":1792806975089,"version":"4.5.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["MLP2008"],"award-info":[{"award-number":["MLP2008"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"DST | Science and Engineering Research Board","doi-asserted-by":"publisher","award":["GAP0232"],"award-info":[{"award-number":["GAP0232"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:p>\n                    Melanocyte development involves key pathways that are often recapitulated during melanoma initiation, highlighting the importance of understanding these regulatory processes. Our study identifies\n                    <jats:italic toggle=\"yes\">mgat4b<\/jats:italic>\n                    , a glycosyl transferase involved in selective\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -glycan branching enriched in pigment progenitors, as a regulator of directional cell migration and establishment of melanocyte stem cell (McSC) pool during early development. Single cell RNA (scRNA) sequencing analysis in zebrafish upon targeted disruption of\n                    <jats:italic toggle=\"yes\">mgat4b<\/jats:italic>\n                    reveals, that migratory melanocyte progenitors marked by galectin expression fail to persist. Lectin affinity proteomic analysis reveals the glycosylation of key melanocyte proteins GPNMB, KIT, and TYRP1 to be under the control of MGAT4B in melanocytic cells. Additionally, mislocalization of Junctional plakoglobin (JUP) explains the observed defects in cell adhesion and migration to be regulated by MGAT4B but not its isozyme MGAT4A. Our meta-analysis further reveals that melanoma patients with both the BRAF\n                    <jats:sup>V600E<\/jats:sup>\n                    mutation and elevated MGAT4B levels have significantly worse survival outcomes compared to those with only the BRAF\n                    <jats:sup>V600E<\/jats:sup>\n                    mutation. By leveraging the zebrafish MAZERATI platform to model BRAF\n                    <jats:sup>V600E<\/jats:sup>\n                    driver mutation in vivo, we show that\n                    <jats:italic toggle=\"yes\">mgat4b<\/jats:italic>\n                    mutant cells fail to aggregate and initiate tumors. RNA profiling of the transformed melanocytes revealed cell\u2013cell junction, adhesion, and ECM binding to be probable contributing factors that resulted in the failure of tumor onset. Using a small-molecule inhibitor we demonstrate that complex\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -glycosylation inhibits early-stage melanoma progression. Our study underscores the importance of selective\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -glycan branching in both melanocyte development and melanoma initiation, suggesting MGAT4B as a promising therapeutic target for melanoma treatment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2423831122","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:23:38Z","timestamp":1748348618000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Mgat4b-mediated selective\n                    <i>N<\/i>\n                    -glycosylation regulates melanocyte development and melanoma progression"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8705-3217","authenticated-orcid":false,"given":"Babita","family":"Sharma","sequence":"first","affiliation":[{"name":"Council of Scientific and Industrial 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India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7583-6392","authenticated-orcid":false,"given":"Ayesha","family":"Nasreen","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology","place":["New Delhi, India"]},{"name":"Academy of Scientific and Innovative Research","place":["Ghaziabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6587-3393","authenticated-orcid":false,"given":"Ayush","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology","place":["New Delhi, India"]},{"name":"Academy of Scientific and Innovative Research","place":["Ghaziabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7822-5731","authenticated-orcid":false,"given":"Yogaspoorthi J.","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology","place":["New Delhi, India"]},{"name":"Academy of Scientific and Innovative Research","place":["Ghaziabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyashri","family":"Rengaraju","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology","place":["New Delhi, India"]},{"name":"Academy of Scientific and Innovative Research","place":["Ghaziabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5679-9910","authenticated-orcid":false,"given":"Srashti Jyoti","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology","place":["New Delhi, India"]},{"name":"Academy of Scientific and Innovative Research","place":["Ghaziabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayank","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhashkar","family":"Paul","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koushika","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial 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