INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Centre of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France.
LabEx DEVweCAN, Université de Lyon, Lyon, France.
Cancer Sci. 2022 Jul;113(7):2214-2223. doi: 10.1111/cas.15389. Epub 2022 May 24.
Numerous epithelial-mesenchymal transition (EMT) characteristics have now been demonstrated to participate in tumor development. Indeed, EMT is involved in invasion, acquisition of stem cell properties, and therapy-associated resistance of cancer cells. Together, these mechanisms offer advantages in adapting to changes in the tumor microenvironment. However, recent findings have shown that EMT-associated transcription factors (EMT-TFs) may also be involved in DNA repair. A better understanding of the coordination between the DNA repair pathways and the role played by some EMT-TFs in the DNA damage response (DDR) should pave the way for new treatments targeting tumor-specific molecular vulnerabilities, which result in selective destruction of cancer cells. Here we review recent advances, providing novel insights into the role of EMT in the DDR and repair pathways, with a particular focus on the influence of EMT on cellular sensitivity to damage, as well as the implications of these relationships for improving the efficacy of cancer treatments.
目前已经证实，许多上皮-间充质转化（EMT）特征参与了肿瘤的发展。事实上，EMT 参与了癌细胞的侵袭、获得干细胞特性和与治疗相关的耐药性。这些机制共同为适应肿瘤微环境的变化提供了优势。然而，最近的研究结果表明，EMT 相关转录因子（EMT-TFs）也可能参与 DNA 修复。更好地理解 DNA 修复途径之间的协调以及一些 EMT-TFs 在 DNA 损伤反应（DDR）中的作用，应该为针对肿瘤特异性分子脆弱性的新治疗方法铺平道路，从而选择性地破坏癌细胞。在这里，我们回顾了最近的进展，为 EMT 在 DDR 和修复途径中的作用提供了新的见解，特别关注 EMT 对细胞对损伤敏感性的影响，以及这些关系对提高癌症治疗效果的意义。
