The Journal of clinical investigation · 2021
FOXA1 overexpression suppresses interferon signaling and immune response in cancer.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
He Yundong, Wang Liguo, Wei Ting, Xiao Yu-Tian, Sheng Haoyue, Su Hengchuan, Hollern Daniel P, Zhang Xiaoling, Ma Jian, Wen Simeng, Xie Hongyan, Yan Yuqian, Pan Yunqian, Hou Xiaonan, Tang Xiaojia, Suman Vera J, Carter Jodi M, Weinshilboum Richard, Wang Liewei, Kalari Krishna R, Weroha Saravut J, Bryce Alan H, Boughey Judy C, Dong Haidong, Perou Charles M, Ye Dingwei, Goetz Matthew P, Ren Shancheng, Huang Haojie
Аннотация
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.