通过雄激素受体 (AR) 的雄激素信号传导对于前列腺肿瘤的发生至关重要。然而，雄激素信号通路还与其他生长因子介导的信号通路相互作用，在前列腺癌的发生和进展过程中调节前列腺细胞周期、分化、凋亡和增殖。胰岛素样生长因子 1 (IGF1) 是前列腺肿瘤发生中最重要的生长因子之一。临床和实验证据表明，IGF1 信号传导支持雄激素依赖性和雄激素非依赖性前列腺肿瘤发生，这表明加深对 IGF1 和雄激素轴之间相互作用的了解可能有助于开发新的治疗策略。现有数据显示雄激素-AR信号传导在IGF1信号通路激活中的动态作用，通过增强前列腺基底上皮细胞中IGF1受体的转录以及通过抑制前列腺基质中IGF结合蛋白3的表达来增加IGF1分泌细胞。反过来，IGF1 刺激前列腺基底祖细胞中的 Wnt-β-连环蛋白信号传导，促进前列腺癌转化和前列腺癌的发展。这些发现强调了雄激素和 IGF1 致癌作用背后的合作、自分泌和旁分泌相互作用，并为治疗靶向开辟了新的机会。© 2024。Springer Nature Limited。

Androgen signalling through the androgen receptor (AR) is essential for prostate tumorigenesis. However, androgen signalling pathways also interact with other growth factor-mediated signalling pathways to regulate the prostatic cell cycle, differentiation, apoptosis and proliferation in the initiation and progression of prostate cancer. Insulin-like growth factor 1 (IGF1) is one of the most prominent growth factors in prostate tumorigenesis. Clinical and experimental evidence has demonstrated that IGF1 signalling supports both androgen-dependent and androgen-independent prostate tumorigenesis, suggesting that improved understanding of the interactions between the IGF1 and androgen axes might aid the development of new therapeutic strategies. Available data have shown a dynamic role of androgen-AR signalling in the activation of IGF1-signalling pathways by augmenting transcription of the IGF1 receptor in prostatic basal epithelial cells and by increasing IGF1 secretion through the suppression of IGF-binding protein 3 expression in prostatic stromal cells. In turn, IGF1 stimulates Wnt-β-catenin signalling in prostatic basal progenitors to promote prostatic oncogenic transformation and prostate cancer development. These findings highlight the cooperative, autocrine and paracrine interactions that underlie the oncogenic effects of androgens and IGF1 and open up new opportunities for therapeutic targeting.© 2024. Springer Nature Limited.