{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:59:22Z","timestamp":1790207962599,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T00:00:00Z","timestamp":1539302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Instituto de Salud Carlos III-FIS\/FEDER","award":["PI14\/00900"],"award-info":[{"award-number":["PI14\/00900"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Squamous epithelia of the head and neck undergo continuous cell renewal and are continuously exposed to mutagenic hazard, the main cause of cancer. How they maintain homeostasis upon cell cycle deregulation is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To elucidate how head and neck epithelia respond to cell cycle stress, we studied human keratinocytes from various locations (oral mucosa, tonsil, pharynx, larynx, and trachea). We made use of genotoxic or mitotic drugs (doxorubicin [DOXO], paclitaxel, and nocodazole), or chemical inhibitors of the mitotic checkpoint kinases, Aurora B and polo\u2010like\u20101. We further tested the response to inactivation of p53, ectopic cyclin E, or to the chemical carcinogen 7,12\u2010dimethylbenz[a]anthracene (DMBA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All treatments provoked DNA damage or mitosis impairment and strikingly triggered squamous differentiation and polyploidization, resulting in irreversible loss of clonogenic capacity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Keratinocytes from head and neck epithelia share a cell\u2010autonomous squamous DNA damage\u2010differentiation response that is common to the epidermis and might continuously protect them from cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.25376","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T08:50:27Z","timestamp":1539334227000},"page":"2487-2497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Response of head and neck epithelial cells to a DNA damage\u2010differentiation checkpoint involving polyploidization"],"prefix":"10.1002","volume":"40","author":[{"given":"Natalia","family":"Sanz\u2010G\u00f3mez","sequence":"first","affiliation":[{"name":"Cell Cycle, Stem Cell Fate and Cancer Laboratory Institute for Research of Marqu\u00e9s de Valdecilla (IDIVAL) Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Freije","sequence":"additional","affiliation":[{"name":"Cell Cycle, Stem Cell Fate and Cancer Laboratory Institute for Research of Marqu\u00e9s de Valdecilla (IDIVAL) Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ceballos","sequence":"additional","affiliation":[{"name":"Cell Cycle, Stem Cell Fate and Cancer Laboratory Institute for Research of Marqu\u00e9s de Valdecilla (IDIVAL) Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Obeso","sequence":"additional","affiliation":[{"name":"Cell Cycle, Stem Cell Fate and Cancer Laboratory Institute for Research of Marqu\u00e9s de Valdecilla (IDIVAL) Santander Spain"},{"name":"Otorhinolaryngology Unit Valdecilla Hospital HUVM Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Ram\u00f3n","family":"Sanz","sequence":"additional","affiliation":[{"name":"Cell Cycle, Stem Cell Fate and Cancer Laboratory Institute for Research of Marqu\u00e9s de Valdecilla (IDIVAL) Santander Spain"},{"name":"Plastic Surgery Unit Valdecilla Hospital HUVM Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fe","family":"Garc\u00eda\u2010Reija","sequence":"additional","affiliation":[{"name":"Cell Cycle, Stem Cell Fate and Cancer Laboratory Institute for Research of Marqu\u00e9s de Valdecilla (IDIVAL) Santander Spain"},{"name":"Oral and Maxillofacial Surgery Unit Valdecilla Hospital HUVM Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Morales\u2010Angulo","sequence":"additional","affiliation":[{"name":"Cell Cycle, Stem Cell Fate and Cancer Laboratory Institute for Research of Marqu\u00e9s de Valdecilla (IDIVAL) Santander Spain"},{"name":"Otorhinolaryngology Unit Valdecilla Hospital HUVM Santander 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