Azbazdar Yagmur, Sosa Eric A, Monka Julia, Kurmangaliyev Yerbol Z, Tejeda-Muñoz Nydia
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, 90095-1662, USA.
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Heliyon. 2024 Jun 2;10(11):e32243. doi: 10.1016/j.heliyon.2024.e32243. eCollection 2024 Jun 15.
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.
Wnt信号通路是最古老且关键的信号级联反应之一,调控着发育和癌症调节中的多种过程。在癌症治疗领域,由于金雀异黄素对包括Wnt通路在内的各种信号通路具有多方面的调节作用,它成为了一个有前景的候选药物。尽管临床前研究成果喜人,但金雀异黄素通过Wnt调节发挥治疗作用的确切机制仍不清楚。在本研究中,我们通过阐明金雀异黄素通过巨胞饮作用对Wnt信号的抑制作用,揭示了其治疗机制的新见解。此外,我们证明了它在SW480结肠腺癌细胞模型中抑制细胞生长、增殖和溶酶体活性的能力。此外,我们的研究扩展到胚胎环境,在那里金雀异黄素影响由内源性Wnt通路控制的基因调控网络。我们的发现揭示了金雀异黄素、Wnt信号、膜运输和基因调控之间的复杂相互作用,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。