Tripathi Sneha, Gupta Ekta, Naik Rutika, Khare Satyajeet, Mir Rafeeq, Kamat Siddhesh, Galande Sanjeev
Laboratory of Chromatin Biology and Epigenetics, Indian Institute of Science Education and Research, Pune 411008, India.
Center of Excellence in Epigenetics, Department of Life Sciences, Shiv Nadar Institution of Eminence, Delhi-NCR, India.
Oncotarget. 2025 Jul 21;16:562-581. doi: 10.18632/oncotarget.28755.
Colorectal cancer remains the second leading cause of cancer-related deaths worldwide, highlighting the urgent need for more effective therapies and a deeper understanding of its molecular basis. Drug repurposing has gained traction as a viable strategy to target dysregulated oncogenic pathways. Statins, commonly prescribed for lowering cholesterol, have recently shown potential anti-cancer effects. In this study, we explore how statin treatment influences lipid metabolism, gene expression, and proteomic profiles in colorectal cancer models. Our findings provide direct evidence that statins selectively modulate key components of the Wnt/β-catenin signaling pathway, a major driver of adenoma formation, including members of the special AT-rich sequence-binding (SATB) protein family. We show that statin treatment downregulates SATB1, a known promoter of tumorigenesis in the context of Wnt activation, while simultaneously upregulating SATB2, which plays an opposing role. This reciprocal regulation shifts cellular phenotypes between epithelial and mesenchymal states in 3D spheroid models. Together, these results highlight the therapeutic potential of statins in colorectal cancer and support their consideration in drug repurposing approaches.
结直肠癌仍然是全球癌症相关死亡的第二大主要原因，这凸显了对更有效治疗方法的迫切需求以及对其分子基础的更深入理解。药物重新利用作为一种针对失调致癌途径的可行策略已受到关注。他汀类药物通常用于降低胆固醇，最近已显示出潜在的抗癌作用。在本研究中，我们探讨了他汀类药物治疗如何影响结直肠癌模型中的脂质代谢、基因表达和蛋白质组学特征。我们的研究结果提供了直接证据，表明他汀类药物选择性地调节Wnt/β-连环蛋白信号通路的关键成分，Wnt/β-连环蛋白信号通路是腺瘤形成的主要驱动因素，包括富含AT序列结合（SATB）蛋白家族的成员。我们表明，他汀类药物治疗下调SATB1，SATB1是Wnt激活背景下已知的肿瘤发生促进因子，同时上调起相反作用的SATB2。这种相互调节在三维球体模型中使细胞表型在上皮状态和间充质状态之间转变。总之，这些结果突出了他汀类药物在结直肠癌中的治疗潜力，并支持在药物重新利用方法中考虑使用它们。
