上皮-间质转化在结直肠癌转移和进展中的作用:分子机制与治疗策略

Epithelial-mesenchymal transition in colorectal cancer metastasis and progression: molecular mechanisms and therapeutic strategies.

作者信息

Nie Fangfang, Sun Xue, Sun Jizhuo, Zhang Jingdong, Wang Yuanhe

机构信息

Liaoning University of Traditional Chinese Medicine, Huanggu District, Shenyang, Liaoning, China.

Medical Oncology Department of Gastrointestinal Cancer, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China.

出版信息

Cell Death Discov. 2025 Jul 22;11(1):336. doi: 10.1038/s41420-025-02593-8.

Abstract

Colorectal cancer (CRC) continues to be a major contributor to cancer-associated death, with metastatic disease posing substantial therapeutic challenges. The epithelial-mesenchymal transition (EMT) orchestrates the transformation of polarized epithelial cells into motile mesenchymal phenotypes, characterized by enhanced migratory capacity and invasive properties. EMT is central to CRC metastasis and progression, particularly concerning its contribution to invasion, internal infiltration, and colonization. Beyond metastasis, EMT facilitates cancer cells' adaptation to diverse microenvironments, gain of stem cell-like characteristics, metabolic reprogramming, and evasion of therapeutic interventions. EMT signatures are emerging as potential prognostic biomarkers, offering valuable insights for real-time disease surveillance and personalized therapeutic strategies. Targeting EMT presents a promising therapeutic avenue to improve drug sensitivity and counteract resistance in CRC. This review systematically examines the molecular mechanisms regulating EMT in CRC, including key transcription factors; post-translational and epigenetic modifications; non-coding RNAs; and pivotal signaling pathways. Additionally, we evaluate the clinical implications of EMT in CRC progression and metastasis and critically assess emerging therapeutic strategies targeting EMT. This study lays the groundwork for developing more efficient interventions to mitigate metastasis and enhance treatment outcomes and patient survival by elucidating the intricate molecular networks that govern EMT and its contributions to CRC pathology.

摘要

结直肠癌(CRC)仍然是癌症相关死亡的主要原因,转移性疾病带来了巨大的治疗挑战。上皮-间质转化(EMT)协调极化上皮细胞向具有运动能力的间质表型转变,其特征是迁移能力和侵袭特性增强。EMT是CRC转移和进展的核心,特别是在其对侵袭、内部浸润和定植的作用方面。除了转移,EMT还促进癌细胞适应多种微环境、获得干细胞样特征、代谢重编程以及逃避治疗干预。EMT特征正成为潜在的预后生物标志物,为实时疾病监测和个性化治疗策略提供有价值的见解。靶向EMT为提高CRC的药物敏感性和对抗耐药性提供了一条有前景的治疗途径。本综述系统地研究了调节CRC中EMT的分子机制,包括关键转录因子;翻译后和表观遗传修饰;非编码RNA;以及关键信号通路。此外,我们评估了EMT在CRC进展和转移中的临床意义,并批判性地评估了针对EMT的新兴治疗策略。本研究通过阐明控制EMT及其对CRC病理学贡献的复杂分子网络,为开发更有效的干预措施以减轻转移、提高治疗效果和患者生存率奠定了基础。

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