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Review
. 2023 May-Jun;25(3):287-295.
doi: 10.4103/aja202259.

FOXA1 in prostate cancer

Hui-Yu Dong  1   2 , Lei Ding  1 , Tian-Ren Zhou  1 , Tao Yan  1 , Jie Li  1 , Chao Liang  1
Affiliations
Review 回顾

FOXA1 in prostate cancer  前列腺癌中的 FOXA1

Hui-Yu Dong et al. Asian J Androl. 2023 May-Jun.
Hui-Yu Dong 亚洲 J Androl2023 5-6 月

Abstract  抽象

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.
大多数前列腺癌最初对雄激素剥夺疗法 （ADT） 有反应。随着 ADT 的长期应用，局限性前列腺癌将发展为去势抵抗性前列腺癌 （CRPC） 、转移性 CRPC （mCRPC） 和神经内分泌前列腺癌 （NEPC），并且转录网络发生了转移。叉头盒蛋白 A1 （FOXA1） 可能通过多种机制在此过程中发挥关键作用。为了更好地了解 FOXA1 在前列腺癌中的作用，我们回顾了 FOXA1 靶向基因、FOXA1 调节剂和 FOXA1 之间的相互作用，特别强调雄激素受体 （AR） 功能。此外，我们讨论了 FOXA1 突变在前列腺癌中的独特作用和 FOXA1 的临床意义。我们总结了 FOXA1 在前列腺癌不同阶段的可能调控途径。我们专注于 FOXA1 和 AR 之间的联系，它们可能在各种类型的前列腺癌中发挥不同的作用。最后，我们讨论了 FOXA1 突变及其在前列腺癌中的临床意义。FOXA1 通过多种途径调节前列腺癌的发展，可能是 mCRPC 和 NEPC 的生物标志物。未来的工作需要集中在晚期前列腺癌中 FOXA1 突变的潜在机制。我们相信 FOXA1 将成为前列腺癌的预后标志物和治疗靶点。

Keywords: androgen receptor; forkhead box protein A1; mutation; prostate cancer.
关键词：雄激素受体;叉头盒蛋白 A1;突变;前列腺癌。

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Figures  数字

Figure 1
Figure 1
Structure of FOXA1 and classes of FOXA1 alterations. FOXA1: forkhead box protein A1; RD: regulatory domain.
Figure 2
Figure 2
FOXA1 and AR-regulated pathway in AR-dependent prostate cancer and AR-independent prostate cancer. (a) Class 1 mutant FOXA1/wild-type FOXA1, opens the closed chromatin and recruits AR to promote oncogenic AR signaling. (b) In AR-independent prostate cancer, mutant FOXA1/wild-type FOXA1 reprograms or replaces AR function, and promotes AR-independent growth. FOXA1: forkhead box protein A1; Wnt: wingless-type MMTV integration site family; AR: androgen receptor; ARE: androgen-receptor response element; EMT: epithelial–mesenchymal transition.
Figure 3
Figure 3
Pathways of FOXA1 involved in different types of prostate cancer. EMT: epithelial–mesenchymal transition; IFN: interferon; CRPC: castration-resistant prostate cancer; NEPC: neuroendocrine prostate cancer; FOXA1: forkhead box protein A1; TMPRSS2: transmembrane protease serine 2; PRCAT38: prostate cancer-associated transcript 38; NKX3-1: NK3 homeobox 1; DSCAM-AS1: DSCAM antisense RNA 1; TGFB3: transforming growth factor-beta 3; IL-8: interleukin 8; SNAI2: snail family transcriptional repressor 2; IGFBP-3: insulin-like growth factor binding protein 3; AR: androgen receptor; STAT2: signal transducer and activator of transcription 2; TLE3: TLE family member 3; HDAC7: histone deacetylase; NFIC: nuclear Factor I C; OC2: ONECUT2; LSD1: histone lysine-specific demethylase 1; OCT4: octamer-binding transcription factor 4; XPO1: nuclear export protein exportin-1; miR-194: microRNA-194; NKX2-1: NK2 homeobox 1; ASCL1: achaete-scute family BHLH transcription factor 1; EZH2: enhancer of zeste 2 polycomb repressive complex 2 subunit; EGF: epidermal growth factor; AR: androgen receptor; lncRNA: long noncoding RNA; miRNA: microRNA; CHGA: chromogranin A.
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