{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:27:17Z","timestamp":1777998437048,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["307111"],"award-info":[{"award-number":["307111"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The transcription factor SOX9 is a key regulator of multiple developmental processes and is frequently re\u2010expressed in non\u2010small cell lung cancer (NSCLC). Its precise role in the progression of NSCLC histotypes has, however, remained elusive. We show that SOX9 expression relates to poor overall survival and invasive histopathology in human non\u2010mucinous adenocarcinoma and is absent in murine early minimally invasive and low in human\n                    <jats:italic>in situ<\/jats:italic>\n                    adenocarcinoma. Interestingly, despite wide SOX9 expression across advanced NSCLC histotypes, its genetic deletion in the murine\n                    <jats:italic>Kras<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>G12D<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>;Lkb1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>fl\/fl<\/jats:italic>\n                    <\/jats:sup>\n                    model selectively disrupted only the growth of papillary NSCLC, without affecting the initiation of precursor lesions or growth of mucinous or squamous tissue. Spatial tissue phenotyping indicated a requirement of SOX9 expression for the progression of surfactant protein C\u2010expressing progenitor cells, which gave rise to papillary tumours. Intriguingly, while SOX9 expression was dispensable for squamous tissue formation, its loss in fact led to enhanced squamous tumour metastasis, which was associated with altered collagen IV deposition in the basement membrane. Our work therefore demonstrates histopathology\u2010selective roles for SOX9 in NSCLC progression, namely as a promoter for papillary adenocarcinoma progression, but an opposing metastasis\u2010suppressing role in squamous histotype tissue. This attests to a pleiotropic SOX9 function, linked to the cell of origin and microenvironmental tissue contexts. \u00a9 2021 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5733","type":"journal-article","created":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T09:31:35Z","timestamp":1621675895000},"page":"16-29","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>SOX9<\/scp>\n                    has distinct roles in the formation and progression of different non\u2010small cell lung cancer histotypes"],"prefix":"10.1002","volume":"255","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-7309","authenticated-orcid":false,"given":"Jie","family":"Bao","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine Finland, HiLIFE University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"N\u00e4rhi","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, HiLIFE University of Helsinki  Helsinki Finland"},{"name":"GlaxoSmithKline  Espoo Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Teod\u00f2sio","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annabrita","family":"Hemmes","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, HiLIFE University of Helsinki  Helsinki 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