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The\n                    <jats:italic>MUC1<\/jats:italic>\n                    gene appeared in mammals to protect barrier tissues from viral infections. There is no known involvement of the\n                    <jats:italic>MUC1<\/jats:italic>\n                    encoded MUC1-C\/M1C protein in the regulation of A3s. We found that induction of MUC1-C in NSCLC cells treated with EGFR inhibitors integrates activation of an inflammatory memory response with the type I interferon (IFN) STAT1\/STAT2\/IRF9 (U-ISGF3) pathway. In turn, MUC1-C drives expression of A3 genes by activating their U-ISGF3-stimulated response elements (ISREs). We also report that MUC1-C-mediated induction of type II IFN STAT1 homodimer (U-GAF) complexes and the gamma-associated signaling (GAS) pathway drives human endogenous retrovirus HERV-K102\/K108 expression. Our results in NSCLC cell line and patient-derived models further demonstrate that MUC1-C activates A3 and HERV-K expression by a common MUC1-C\u2192STAT1 auto-inductive pathway. These previously unrecognized findings demonstrate that a MUC1-C-driven inflammatory pathway coordinates activation of APOBEC3 and HERV-K expression.\n                  <\/jats:p>","DOI":"10.1038\/s41420-025-02673-9","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T10:35:34Z","timestamp":1754649334000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Activation of APOBEC3 cytidine deaminases and endogenous retroviruses is integrated by MUC1-C in NSCLC cells"],"prefix":"10.1038","volume":"11","author":[{"given":"Naoki","family":"Haratake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinkichi","family":"Takamori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0124-996X","authenticated-orcid":false,"given":"Hideko","family":"Isozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Shigeta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Kikutake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3771-7940","authenticated-orcid":false,"given":"Hiroki","family":"Ozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atrayee","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2443-6995","authenticated-orcid":false,"given":"Ayako","family":"Nakashoji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9526-3193","authenticated-orcid":false,"given":"Mikita","family":"Suyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyoshi","family":"Takenaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4497-1816","authenticated-orcid":false,"given":"Tomoharu","family":"Yoshizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Osoegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6127-318X","authenticated-orcid":false,"given":"Aaron N.","family":"Hata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5743-8888","authenticated-orcid":false,"given":"Donald","family":"Kufe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"2673_CR1","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1073\/pnas.1914183116","volume":"117","author":"J Ito","year":"2020","unstructured":"Ito J, Gifford RJ, Sato K. 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