{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T05:26:14Z","timestamp":1770182774925,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2022R1A2C1003498"],"award-info":[{"award-number":["NRF-2022R1A2C1003498"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-25414953"],"award-info":[{"award-number":["RS-2025-25414953"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Fellowship Foundation"},{"name":"KHU Medical Research Fund from Kyung Hee University","award":["KHU-20252708"],"award-info":[{"award-number":["KHU-20252708"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ovarian cancer remains the most lethal gynecological malignancy, largely due to its early dissemination and extensive peritoneal metastasis. The tumor microenvironment (TME), particularly tumor-associated macrophages, promotes this invasive phenotype; however, the precise molecular effectors linking immune-to-tumor signaling remain unclear. We identified FRY, a microtubule-binding protein previously uncharacterized in ovarian pathology, as a critical mediator of macrophage-driven invasion. We observed that conditioned medium from ovarian cancer-stimulated macrophages (OCM) robustly induced FRY expression in ovarian cancer cells. Clinically, elevated FRY levels correlate with advanced tumor stage and poor patient survival. Functionally, FRY knockdown significantly abrogated OCM-induced invasion without affecting cell viability, highlighting its specific role in motility. Mechanistically, FRY facilitates epithelial\u2013mesenchymal transition (EMT) and acts as an essential downstream effector of the PI3K\/AKT signaling cascade; notably, FRY was required for AKT1-driven invasive behaviors. Furthermore, we identified the transcription factor NFIX as a key regulator of FRY expression. Macrophage-derived signals upregulate NFIX, which directly regulates FRY transcription. Pharmacological inhibition of the CXCR1\/2 axis with reparixin effectively blocked OCM-mediated induction of both NFIX and FRY, suggesting that chemokine signaling initiates this pro-invasive loop. Collectively, these findings suggest that FRY is a macrophage-driven mediator of invasion and underscore its potential relevance in ovarian cancer.<\/jats:p>","DOI":"10.3390\/cells15030289","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:46:28Z","timestamp":1770137188000},"page":"289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FRY Mediates THP1-Driven Ovarian Cancer Invasion Through the PI3K\/AKT Pathway"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9282-3922","authenticated-orcid":false,"given":"Jin-Hyung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Integrated Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-1478","authenticated-orcid":false,"given":"Jae-Yoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo-Yeon","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Yeon","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, College of Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-6814","authenticated-orcid":false,"given":"Jung-Hye","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Integrated Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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