{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:15:54Z","timestamp":1783595754197,"version":"3.55.0"},"reference-count":104,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute of the National Institutes of Health","award":["CA97098"],"award-info":[{"award-number":["CA97098"]}]},{"name":"National Cancer Institute of the National Institutes of Health","award":["CA282437"],"award-info":[{"award-number":["CA282437"]}]},{"name":"National Cancer Institute of the National Institutes of Health","award":["CA289134"],"award-info":[{"award-number":["CA289134"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The MUCIN 1 (MUC1) gene evolved in eutherian mammals in association with the marked expansion of endogenous retroviruses (ERVs). MUC1 encodes the MUC1-C\/M1C protein that protects barrier epithelia from exogenous viruses. Activation of M1C in response to loss of homeostasis induces STAT1 and the type I interferon (IFN-I) pathway. Studies in cancer cells have found that M1C regulates human ERV (HERV) expression by a STAT1-mediated mechanism. These discoveries have uncovered new insights into M1C-induced regulation of HERVs and other retrotransposons, such as LINE-1 (L1) and Alu. M1C signaling integrates retrotransposon transcription with induction of the counteracting apolipoprotein B mRNA-editing catalytic 3 (APOBEC3) genes that, like MUC1, first appeared in placental mammals. Activation of retrotransposons induces viral mimicry characterized as an IFN-I response that promotes innate anti-tumor immunity. Conversely, M1C protects cancer cells by sustained induction of the IFN-I pathway and immune evasion. This review posits that M1C-dependent regulation of retrotransposon and APOBEC3 expression represents an adaptive response exploited by cancer cells that promotes malignant progression.<\/jats:p>","DOI":"10.3390\/ijms27146135","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:16:22Z","timestamp":1783592182000},"page":"6135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolution of MUC1 During Retrotransposon Expansion as a Potential Adaptation Exploited in Human Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Naoki","family":"Haratake","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, D830, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinkichi","family":"Takamori","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, D830, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Shigeta","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, D830, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5743-8888","authenticated-orcid":false,"given":"Donald","family":"Kufe","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, D830, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41579-019-0189-2","article-title":"Origins and evolutionary consequences of ancient endogenous retroviruses","volume":"17","author":"Johnson","year":"2019","journal-title":"Nat. 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