PDF(Pubmed)
Abstract：
The Wnt signaling pathway is one of the most ancient and pivotal signaling cascades, governing diverse processes in development and cancer regulation. Within the realm of cancer treatment, genistein emerges as a promising candidate due to its multifaceted modulation of various signaling pathways, including the Wnt pathway. Despite promising preclinical studies, the precise mechanisms underlying genistein\'s therapeutic effects via Wnt modulation remain elusive. In this study, we unveil novel insights into the therapeutic mechanisms of genistein by elucidating its inhibitory effects on Wnt signaling through macropinocytosis. Additionally, we demonstrate its capability to curtail cell growth, proliferation, and lysosomal activity in the SW480 colon adenocarcinoma cell model. Furthermore, our investigation extends to the embryonic context, where genistein influences gene regulatory networks governed by endogenous Wnt pathways. Our findings shed light on the intricate interplay between genistein, Wnt signaling, membrane trafficking, and gene regulation, paving the way for further exploration of genistein\'s therapeutic potential in cancer treatment strategies.
摘要：
Wnt信号通路是最古老和最关键的信号级联之一，管理发育和癌症调节的不同过程。在癌症治疗领域，金雀异黄素由于其对各种信号通路的多方面调节而成为有前途的候选者，包括Wnt通路。尽管有希望的临床前研究，金雀异黄素通过Wnt调节的治疗效果的确切机制仍然难以捉摸。在这项研究中,我们揭示了金雀异黄素的治疗机制的新见解，阐明了它对Wnt信号的抑制作用。此外,我们证明了它抑制细胞生长的能力，扩散,SW480结肠腺癌细胞模型中的溶酶体活性。此外，我们的调查延伸到胚胎背景，其中金雀异黄素影响由内源性Wnt途径控制的基因调控网络。我们的发现揭示了金雀异黄素之间复杂的相互作用，Wnt信号,膜贩运，和基因调控，为进一步探索金雀异黄素在癌症治疗策略中的治疗潜力铺平了道路。
