{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T18:27:51Z","timestamp":1783794471248,"version":"3.55.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5P30CA045508"],"award-info":[{"award-number":["5P30CA045508"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA225134"],"award-info":[{"award-number":["CA225134"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA247400"],"award-info":[{"award-number":["CA247400"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA190997"],"award-info":[{"award-number":["R01CA190997"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21OD018332"],"award-info":[{"award-number":["R21OD018332"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013356","name":"Cold Spring Harbor Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013356","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Northwell Health Affiliation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The chromobox-containing protein CBX4 is an important regulator of epithelial cell proliferation and differentiation, and has been implicated in several cancer types. The cancer stem cell (CSC) population is a key driver of metastasis and recurrence. The undifferentiated, plastic state characteristic of CSCs relies on cues from the microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the microenvironment that can influence the CSC population through the secretion of extracellular matrix and a variety of growth factors. Here we show CBX4 is a critical regulator of the CSC phenotype in squamous cell carcinomas of the skin and hypopharynx. Moreover, CAFs can promote the expression of CBX4 in the CSC population through the secretion of interleukin-6 (IL-6). IL-6 activates JAK\/STAT3 signaling to increase \u2206Np63\u03b1\u2014a key transcription factor that is essential for epithelial stem cell function and the maintenance of proliferative potential that is capable of regulating CBX4. Targeting the JAK\/STAT3 axis or CBX4 directly suppresses the aggressive phenotype of CSCs and represents a novel opportunity for therapeutic intervention.<\/jats:p>","DOI":"10.1093\/carcin\/bgad048","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T19:20:47Z","timestamp":1689708047000},"page":"485-496","source":"Crossref","is-referenced-by-count":6,"title":["Cancer-associated fibroblasts promote cancer stemness by inducing expression of the chromatin-modifying protein CBX4 in squamous cell carcinoma"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1084-7283","authenticated-orcid":false,"given":"Matthew L","family":"Fisher","sequence":"first","affiliation":[{"name":"Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seamus","family":"Balinth","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724 , USA"},{"name":"Molecular and Cellular Biology Program, Stony Brook University , Stony Brook, NY 11794 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yon","family":"Hwangbo","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caizhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Ballon","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary L","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Zucker School of Medicine, Hofstra University\/Northwell Health , Hempstead, NY 11549 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4416-6646","authenticated-orcid":false,"given":"Alea A","family":"Mills","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"2023110912084575400_CIT0001","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41568-018-0024-5","article-title":"Deciphering the cells of origin of squamous cell carcinomas","volume":"18","author":"S\u00e1nchez-Dan\u00e9s","year":"2018","journal-title":"Nat. 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