Kim Sumin, Han Ho Jin, Han Junyeol, Choi Yerim, Ryoo In-Ja, Sivaraman Aneesh, Lee Kyeong, Kim Bo Yeon, Moon Eun-Yi, Soung Nak-Kyun
Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, 28116, Republic of Korea.
Department of Biomolecular Science, Korea National University of Science and Technology, Daejeon, 34113, Republic of Korea.
Sci Rep. 2025 Jul 1;15(1):21781. doi: 10.1038/s41598-025-05203-w.
Colorectal cancer is a leading cause of cancer-related deaths, with metastasis being the primary contributor to its poor prognosis. Despite the development of various therapeutic strategies, metastatic colorectal cancer prognosis still needs improvement. MO-2097, a novel therapeutic compound, was evaluated for its potential to inhibit metastasis by targeting critical processes such as cancer cell migration and invasion. The ability of MO-2097 to inhibit cancer cell migration was confirmed through wound healing and trans-well migration assays. Further investigation using western blot analysis revealed that MO-2097 inhibited the RAF/MEK/ERK signaling pathway by destabilizing RAF-1, a key regulator of cancer progression and metastasis. Moreover, MO-2097 treatment led to the downregulation of mesenchymal markers N-cadherin and Vimentin while reducing the expression of EMT-related transcription factors such as Snail, Slug, and ZEB1. In a 3D spheroid invasion model, MO-2097 significantly inhibited cancer cell invasion by reducing their ability to penetrate the extracellular matrix. Furthermore, MO-2097 disrupted the vascular network formation in HUVECs, indicating its impact on angiogenesis, a process essential for tumor growth and metastasis. These findings demonstrate MO-2097's promise as both an anti-metastatic and anti-angiogenic agent, offering a novel therapeutic approach for treating metastatic colorectal cancer and emphasizing its potential for future clinical applications.
结直肠癌是癌症相关死亡的主要原因之一，转移是其预后不良的主要因素。尽管已经开发了各种治疗策略，但转移性结直肠癌的预后仍需改善。新型治疗化合物MO-2097通过靶向癌细胞迁移和侵袭等关键过程来评估其抑制转移的潜力。通过伤口愈合和Transwell迁移试验证实了MO-2097抑制癌细胞迁移的能力。使用蛋白质印迹分析的进一步研究表明，MO-2097通过使RAF-1（癌症进展和转移的关键调节因子）不稳定来抑制RAF/MEK/ERK信号通路。此外，MO-2097处理导致间充质标志物N-钙黏蛋白和波形蛋白的下调，同时降低了Snail、Slug和ZEB1等EMT相关转录因子的表达。在三维球体侵袭模型中，MO-2097通过降低癌细胞穿透细胞外基质的能力，显著抑制了癌细胞的侵袭。此外，MO-2097破坏了人脐静脉内皮细胞中的血管网络形成，表明其对血管生成的影响，血管生成是肿瘤生长和转移所必需的过程。这些发现证明了MO-2097作为抗转移和抗血管生成药物的前景，为治疗转移性结直肠癌提供了一种新的治疗方法，并强调了其在未来临床应用中的潜力。
