@article{a82cb6b1ec614e92984a176c46f73d0f,
title = "FOXA1 overexpression suppresses interferon signaling and immune response in cancer",
abstract = "Androgen receptor–positive prostate cancer (PCa) and estrogen receptor–positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients. FOXA1 bound the STAT2 DNA-binding domain and suppressed STAT2 DNA-binding activity, IFN signaling gene expression, and cancer immune response independently of the transactivation activity of FOXA1 and its mutations detected in PCa and BCa. Increased FOXA1 expression promoted cancer immuno- and chemotherapy resistance in mice and PCa and BCa patients. These findings were also validated in bladder cancer expressing high levels of FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal PCa, BCa, and bladder cancer to immuno- and chemotherapy.",
author = "Yundong He and Liguo Wang and Ting Wei and Xiao, {Yu Tian} and Haoyue Sheng and Hengchuan Su and Hollern, {Daniel P.} and Xiaoling Zhang and Jian Ma and Simeng Wen and Hongyan Xie and Yuqian Yan and Yunqian Pan and Xiaonan Hou and Xiaojia Tang and Suman, {Vera J.} and Carter, {Jodi M.} and Richard Weinshilboum and Liewei Wang and Kalari, {Krishna R.} and Weroha, {Saravut J.} and Bryce, {Alan H.} and Boughey, {Judy C.} and Haidong Dong and Perou, {Charles M.} and Dingwei Ye and Goetz, {Matthew P.} and Shancheng Ren and Haojie Huang",
note = "Funding Information: This work was supported in part by National Institutes of Health grants R01 CA130908 and CA203849 (to HH); the Mayo Clinic Foundation (to HH); Mayo Clinic Breast SPORE grant P50CA116201-9 (to MPG, Liewei Wang, KRK, and VJS); Mayo Clinic Cancer Center Support grant P50CA015083; Mayo Clinic Center for Individualized Medicine; Nadia{\textquoteright}s Gift Foundation; John P. Guider; The Eveleigh Family; George M. Eisenberg Foundation for Charities; Prospect Creek Foundation; and the Randy Shaver Cancer Research and Community Fund. YH is supported by a Mayo Clinic Edward C. Kendall Fellowship. Publisher Copyright: {\textcopyright} 2021, American Society for Clinical Investigation.",
year = "2021",
month = jul,
doi = "10.1172/JCI147025",
language = "English (US)",
volume = "131",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "14",
}