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A forkhead box protein O1 (FOXO1) transcription factor is a critical mediator of the cellular responses to oxidative stress in various cell types. However, the roles of FOXO1 in CAFs have been poorly understood. Here, we show more intense FOXO1 staining in stromal fibroblasts in human breast cancers compared to those in non\u2010cancerous regions. Notably, stronger stromal FOXO1 staining is significantly associated with poorer outcomes in 237 breast cancer patients. FOXO1 expression is also more abundant in cultured human breast CAFs compared to the control counterpart human mammary fibroblasts. FOXO1 expression is upregulated in control fibroblasts by malnutrition and hypoxia, suggesting such starvation to mediate increased FOXO1 expression in CAFs. Of note, treatment with AS1842856, a FOXO1 inhibitor, significantly attenuates growth and viability in CAFs relative to control fibroblasts. Suppression of FOXO1 expression by shRNA also substantially inhibits CAFs' growth in culture. When the FOXO1\u2010knockdowned CAFs were implanted with breast cancer cells into recipient mice, the number of these fibroblasts present in developed tumors tends to decrease. Taken together, these findings indicate that FOXO1 expression in human breast CAFs is required for their growth and viability.<\/jats:p>","DOI":"10.1111\/gtc.70133","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T11:26:27Z","timestamp":1782732387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>FOXO1<\/scp>\n                    Is Required for Growth and Viability of Cancer\u2010Associated Fibroblasts in Human Breast Carcinomas"],"prefix":"10.1111","volume":"31","author":[{"given":"Takumi","family":"Koyama","sequence":"first","affiliation":[{"name":"Department of Oral Pathobiological Science and Surgery Tokyo Dental College  Tokyo Japan"},{"name":"Department of Pathology and Oncology Juntendo University Faculty of Medicine  Tokyo 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