<p>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.</p>

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MO-2097 inhibits EMT and angiogenesis in colorectal cancer by targeting RAF/MEK/ERK signaling

  • Sumin Kim,
  • Ho Jin Han,
  • Junyeol Han,
  • Yerim Choi,
  • In-Ja Ryoo,
  • Aneesh Sivaraman,
  • Kyeong Lee,
  • Bo Yeon Kim,
  • Eun-Yi Moon,
  • Nak-Kyun Soung

摘要

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.