上皮-间质可塑性：癌症进展的核心调节因子
Epithelial-Mesenchymal Plasticity: A Central Regulator of Cancer Progression.
作者信息
Ye Xin, Weinberg Robert A
机构信息
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Trends Cell Biol. 2015 Nov;25(11):675-686. doi: 10.1016/j.tcb.2015.07.012. Epub 2015 Oct 1.
Abstract
The epithelial-mesenchymal transition (EMT) program has emerged as a central driver of tumor malignancy. Moreover, the recently uncovered link between passage through an EMT and acquisition of stem-like properties indicates that activation of the EMT programs serves as a major mechanism for generating cancer stem cells (CSCs); that is, a subpopulation of cancer cells that are responsible for initiating and propagating the disease. In this review, we summarize the evidence supporting the widespread involvement of the EMT program in tumor pathogenesis and attempt to rationalize the connection between the EMT program and acquisition of stem cell traits. We propose that epithelial-mesenchymal plasticity is likely controlled by multiple varients of the core EMT program, and foresee the need to resolve the various programs and the molecular mechanisms that underlie them.
摘要
上皮-间质转化（EMT）程序已成为肿瘤恶性发展的核心驱动因素。此外，最近发现的经历EMT与获得干细胞样特性之间的联系表明，EMT程序的激活是产生癌症干细胞（CSCs）的主要机制；也就是说，癌症干细胞是负责启动和传播疾病的癌细胞亚群。在本综述中，我们总结了支持EMT程序广泛参与肿瘤发病机制的证据，并试图阐明EMT程序与获得干细胞特性之间的联系。我们提出上皮-间质可塑性可能由核心EMT程序的多个变体控制，并预见需要解析各种程序及其潜在的分子机制。
相似文献
1
Epithelial-Mesenchymal Plasticity: A Central Regulator of Cancer Progression.上皮-间质可塑性：癌症进展的核心调节因子
Trends Cell Biol. 2015 Nov;25(11):675-686. doi: 10.1016/j.tcb.2015.07.012. Epub 2015 Oct 1.
2
The epithelial-mesenchymal transition and cancer stem cells: functional and mechanistic links.上皮-间质转化与癌症干细胞：功能及机制联系
Curr Pharm Des. 2015;21(10):1279-91. doi: 10.2174/1381612821666141211115611.
3
Involvement of partial EMT in cancer progression.部分 EMT 参与癌症进展。
J Biochem. 2018 Oct 1;164(4):257-264. doi: 10.1093/jb/mvy047.
4
Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial-Mesenchymal Transition.JAK/STAT3信号通路在上皮-间质转化调控肿瘤转移、癌症干细胞转变及肿瘤化疗耐药中的作用
Cells. 2020 Jan 15;9(1):217. doi: 10.3390/cells9010217.
5
HIF-1α induces the epithelial-mesenchymal transition in gastric cancer stem cells through the Snail pathway.缺氧诱导因子-1α通过Snail信号通路诱导胃癌干细胞发生上皮-间质转化。
Oncotarget. 2017 Feb 7;8(6):9535-9545. doi: 10.18632/oncotarget.14484.
6
TGF-β signaling and epithelial-mesenchymal transition in cancer progression.TGF-β 信号通路与癌症进展中的上皮间质转化。
Curr Opin Oncol. 2013 Jan;25(1):76-84. doi: 10.1097/CCO.0b013e32835b6371.
7
Concise Review: Stem Cells and Epithelial-Mesenchymal Transition in Cancer: Biological Implications and Therapeutic Targets.简要综述：癌症中的干细胞与上皮-间质转化：生物学意义及治疗靶点
Stem Cells. 2016 Aug;34(8):1997-2007. doi: 10.1002/stem.2406. Epub 2016 Jun 20.
8
Revisiting epithelial-mesenchymal transition in cancer metastasis: the connection between epithelial plasticity and stemness.重新审视癌症转移中的上皮-间质转化：上皮可塑性与干性之间的联系。
Mol Oncol. 2017 Jul;11(7):792-804. doi: 10.1002/1878-0261.12096. Epub 2017 Jun 26.
9
Intratumoral heterogeneity: Clonal cooperation in epithelial-to-mesenchymal transition and metastasis.肿瘤内异质性：上皮-间质转化和转移中的克隆合作
Cell Adh Migr. 2015;9(4):265-76. doi: 10.4161/19336918.2014.972761. Epub 2014 Oct 16.
10
Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma.癌症干细胞的上皮-间质可塑性：肝细胞癌的治疗靶点
J Hematol Oncol. 2016 Aug 30;9(1):74. doi: 10.1186/s13045-016-0307-9.
引用本文的文献
1
Interplay of oxidative stress and antioxidant mechanisms in cancer development and progression.氧化应激与抗氧化机制在癌症发生和发展中的相互作用。
Arch Toxicol. 2025 Sep 4. doi: 10.1007/s00204-025-04146-5.
2
Perspectives on integrating artificial intelligence and single-cell omics for cellular plasticity research.整合人工智能与单细胞组学用于细胞可塑性研究的展望
Quant Biol. 2025 Dec;13(4). doi: 10.1002/qub2.70004. Epub 2025 Apr 24.
3
Inorganic Polyphosphate Triggers NLRP3 Inflammasome and Promotes the Epithelial-to-Mesenchymal Transition and Migration of Colorectal Cancer Cells Through TRPM8 Receptor.无机多聚磷酸盐通过TRPM8受体触发NLRP3炎性小体并促进结肠癌细胞的上皮-间质转化和迁移。
Int J Mol Sci. 2025 Aug 11;26(16):7743. doi: 10.3390/ijms26167743.
4
Multi-Omic Characterization of Epithelial-Mesenchymal Transition: Lipidomic and Metabolomic Profiles as Key Markers of TGF-β-Induced Transition in Huh7 Hepatocellular Carcinoma.上皮-间质转化的多组学特征：脂质组学和代谢组学图谱作为转化生长因子-β诱导的Huh7肝癌细胞系转化的关键标志物
Cells. 2025 Aug 10;14(16):1233. doi: 10.3390/cells14161233.
5
The role of SOX transcription factors in prostate cancer: Focusing on SOX2.SOX转录因子在前列腺癌中的作用：聚焦于SOX2
Genes Dis. 2025 May 21;12(6):101692. doi: 10.1016/j.gendis.2025.101692. eCollection 2025 Nov.
6
Metastatic heterogeneity in pancreatic cancer: mechanisms and opportunities for targeted intervention.胰腺癌的转移异质性：靶向干预的机制与机遇
J Clin Invest. 2025 Jul 15;135(14). doi: 10.1172/JCI191943.
7
A patient-derived organoid model captures fetal-like plasticity in colorectal cancer.一种源自患者的类器官模型揭示了结直肠癌中类似胎儿的可塑性。
Cell Res. 2025 Jul 4. doi: 10.1038/s41422-025-01139-y.
8
The Role and Function of Non-Coding RNAs in Cholangiocarcinoma Invasiveness.非编码RNA在胆管癌侵袭中的作用与功能
Biomedicines. 2025 Jun 3;13(6):1369. doi: 10.3390/biomedicines13061369.
9
Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer.激光捕获显微切割肿瘤的转录组分析揭示RAD51AP1作为一种与胰腺上皮内瘤变向浸润性胰腺癌进展相关的肿瘤特异性标志物。
Cancer Cell Int. 2025 Jun 10;25(1):208. doi: 10.1186/s12935-025-03810-1.
10
Cisplatin palbociclib combination differentially modulates PTEN AKT signaling via Hsp90 in hepatocellular carcinoma cells.顺铂与帕博西尼联合用药通过热休克蛋白90对肝癌细胞中的PTEN-AKT信号通路产生不同调节作用。
Sci Rep. 2025 Jun 2;15(1):19319. doi: 10.1038/s41598-025-04008-1.
本文引用的文献
1
Stem-cell-like properties and epithelial plasticity arise as stable traits after transient Twist1 activation.在短暂的Twist1激活后，干细胞样特性和上皮可塑性作为稳定特征出现。
Cell Rep. 2015 Jan 13;10(2):131-9. doi: 10.1016/j.celrep.2014.12.032. Epub 2015 Jan 8.
2
Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression.转移是通过微小RNA-200/ZEB1轴对肿瘤细胞程序性死亡受体配体1（PD-L1）表达及肿瘤内免疫抑制的调控来实现的。
Nat Commun. 2014 Oct 28;5:5241. doi: 10.1038/ncomms6241.
3
A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages.由单核细胞和巨噬细胞旁分泌信号支持的乳腺癌干细胞微环境。
Nat Cell Biol. 2014 Nov;16(11):1105-17. doi: 10.1038/ncb3041. Epub 2014 Sep 28.
4
Dihydropyrimidine accumulation is required for the epithelial-mesenchymal transition.上皮-间质转化需要二氢嘧啶的积累。
Cell. 2014 Aug 28;158(5):1094-1109. doi: 10.1016/j.cell.2014.07.032.
5
Transient SNAIL1 expression is necessary for metastatic competence in breast cancer.短暂的SNAIL1表达是乳腺癌转移能力所必需的。
Cancer Res. 2014 Nov 1;74(21):6330-40. doi: 10.1158/0008-5472.CAN-14-0923. Epub 2014 Aug 27.
6
A signature of epithelial-mesenchymal plasticity and stromal activation in primary tumor modulates late recurrence in breast cancer independent of disease subtype.原发性肿瘤中上皮-间质可塑性和基质激活的特征独立于疾病亚型调节乳腺癌的晚期复发。
Breast Cancer Res. 2014 Jul 25;16(4):407. doi: 10.1186/s13058-014-0407-9.
7
Targeting WNT1-inducible signaling pathway protein 2 alters human breast cancer cell susceptibility to specific lysis through regulation of KLF-4 and miR-7 expression.靶向WNT1诱导信号通路蛋白2通过调节KLF-4和miR-7的表达改变人乳腺癌细胞对特异性裂解的敏感性。
Oncogene. 2015 Apr 23;34(17):2261-71. doi: 10.1038/onc.2014.151. Epub 2014 Jun 16.
8
A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis.间充质样癌细胞与巨噬细胞之间的正反馈环对于乳腺癌转移至关重要。
Cancer Cell. 2014 May 12;25(5):605-20. doi: 10.1016/j.ccr.2014.03.021.
9
Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study.早期浸润性乳腺癌中的上皮-间质转化：一项免疫组织化学和反相蛋白质阵列研究
Breast Cancer Res Treat. 2014 Jun;145(2):339-48. doi: 10.1007/s10549-014-2927-5. Epub 2014 Apr 26.
10
TGF-β-Id1 signaling opposes Twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition.转化生长因子-β-Id1信号通路通过间充质-上皮转化对抗Twist1并促进转移定植。
Cell Rep. 2013 Dec 12;5(5):1228-42. doi: 10.1016/j.celrep.2013.11.014.
Zotero 插件