{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:19Z","timestamp":1792790359482,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Cancer Biology","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"American Pediatric Surgical Association Foundation"},{"name":"Kaul Pediatric Research Institute","id":[{"id":"https:\/\/ror.org\/01n0pw264","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Neuroblastoma is the most common extracranial solid tumor of childhood. Its clinical behavior ranges from spontaneous regression to lethal, treatment-refractory disease. Aberrant \u03b12,6-sialylation contributes to aggressive phenotypes in many cancers, but the role of ST6Gal2, a neural-enriched \u03b12,6-sialyltransferase, in neuroblastoma is largely unexplored. Here, we examine the clinical and functional significance of ST6Gal2 in neuroblastoma. In two independent public cohorts (SEQC, n=498; Kocak, n=649), high\n                  <jats:italic>ST6GAL2<\/jats:italic>\n                  expression was associated with significantly worse overall and event-free survival. In the SEQC cohort,\n                  <jats:italic>ST6GAL2<\/jats:italic>\n                  expression was higher in high-risk and\n                  <jats:italic>MYCN<\/jats:italic>\n                  -amplified tumors, varied across International Neuroblastoma Staging System stages, and correlated positively with a mesenchymal transcriptional signature (Spearman \u03c1=0.181). The mesenchymal correlation was reproduced in the Kocak cohort (\u03c1=0.204). Stable shRNA-mediated knockdown of\n                  <jats:italic>ST6GAL2<\/jats:italic>\n                  in SK-N-AS and SK-N-BE(2) cells reduced proliferation and viability, impaired wound closure, and decreased migration and invasion. In preliminary experiments in SK-N-AS cells,\n                  <jats:italic>ST6GAL2<\/jats:italic>\n                  knockdown reduced binding of\n                  <jats:italic>Sambucus nigra<\/jats:italic>\n                  agglutinin, consistent with a role for ST6Gal2 in \u03b12,6-sialylation. Together, these findings link ST6Gal2 expression to aggressive clinical and transcriptional features and pro-tumorigenic phenotypes in neuroblastoma and nominate ST6Gal2-mediated sialylation as a candidate pathway for mechanistic study.\n                <\/jats:p>","DOI":"10.64898\/2026.09.24.754123","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:45:17Z","timestamp":1790588717000},"source":"Crossref","is-referenced-by-count":0,"title":["ST6Gal2 promotes \u03b12,6-sialylation and aggressive phenotypes in neuroblastoma cells"],"prefix":"10.64898","author":[{"given":"Laxmi","family":"Swami","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"},{"name":"Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, 304022, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punarvi","family":"Mandadapu","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayra E.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail R.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pracheta","family":"Janmeda","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, 304022, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin M.","family":"Hardiman","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3952-1017","authenticated-orcid":false,"given":"Laura L.","family":"Stafman","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026093008201194000_2026.09.24.754123v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60983-0"},{"key":"2026093008201194000_2026.09.24.754123v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.soc.2020.11.010"},{"key":"2026093008201194000_2026.09.24.754123v1.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.34.3392"},{"key":"2026093008201194000_2026.09.24.754123v1.4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.4648"},{"key":"2026093008201194000_2026.09.24.754123v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3899"},{"key":"2026093008201194000_2026.09.24.754123v1.6","unstructured":"Bellis SL , Reis CA , Varki A , Kannagi R , Stanley P. Glycosylation Changes in Cancer. In: Varki A , Cummings RD , Esko JD , Stanley P , Hart GW , Aebi M , Mohnen D , Kinoshita T , Packer NH , Prestegard JH , Schnaar RL , Seeberger PH , editors. Essentials of Glycobiology. 4th ed. 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