Garg Minal
Department of Biochemistry, University of Lucknow, Lucknow, 226007, Uttar Pradesh, India.
Cancer Metastasis Rev. 2022 Mar;41(1):131-145. doi: 10.1007/s10555-021-10003-5. Epub 2022 Jan 3.
Strong association of cancer incidence and its progression with mortality highlights the need to decipher the cellular and molecular mechanisms that drive tumor cells to rapidly progress to metastatic disease and therapy resistance. Epithelial-mesenchymal plasticity (EMP) emerged as a key regulator of metastatic outgrowth. It allows neoplastic epithelial cells to delaminate from their neighbors either individually or collectively, traverse the extracellular matrix (ECM) barrier, enter into the circulation, and establish distal metastases. Plasticity between epithelial and mesenchymal states and the existence of hybrid epithelial/mesenchymal (E/M) phenotypes are increasingly being reported in different tumor contexts. Small subset of cancer cells with stemness called cancer stem cells (CSCs) exhibit plasticity, possess high tumorigenic potential, and contribute to high degree of tumoral heterogeneity. EMP characterized by the presence of dynamic intermediate states is reported to be influenced by (epi)genomic reprograming, growth factor signaling, inflammation, and low oxygen generated by tumor stromal microenvironment. EMP alters the genotypic and phenotypic characteristics of tumor cells/CSCs, disrupts tissue homeostasis, induces the reprogramming of angiogenic and immune recognition functions, and renders tumor cells to survive hostile microenvironments and resist therapy. The present review summarizes the roles of EMP in tumor invasion and metastasis and provides an update on therapeutic strategies to target the metastatic and refractory cancers.
癌症发病率及其进展与死亡率之间的强关联凸显了破译驱动肿瘤细胞迅速发展为转移性疾病和治疗抵抗的细胞和分子机制的必要性。上皮-间质可塑性（EMP）已成为转移性生长的关键调节因子。它使肿瘤上皮细胞能够单独或集体从其相邻细胞中脱离，穿越细胞外基质（ECM）屏障，进入循环系统，并形成远处转移。上皮和间质状态之间的可塑性以及混合上皮/间质（E/M）表型的存在在不同肿瘤背景下的报道越来越多。一小部分具有干性的癌细胞，即癌症干细胞（CSCs），表现出可塑性，具有高致瘤潜力，并导致高度的肿瘤异质性。据报道，以动态中间状态的存在为特征的EMP受（表观）基因组重编程、生长因子信号传导、炎症以及肿瘤基质微环境产生的低氧影响。EMP改变肿瘤细胞/CSCs的基因型和表型特征，破坏组织稳态，诱导血管生成和免疫识别功能的重编程，并使肿瘤细胞能够在恶劣的微环境中存活并抵抗治疗。本综述总结了EMP在肿瘤侵袭和转移中的作用，并提供了针对转移性和难治性癌症的治疗策略的最新进展。
