TGF-β在肿瘤微环境中多重作用的研究进展

doi:10.11904/j.issn.1002-3070.2015.05.015

摘要/Abstract

摘要： 转化生长因子β(Transforming growth factor-β,TGF-β)通路在调节细胞生长、分化和迁移中的显著作用决定了该信号通路在癌细胞的进展过程中也具有至关重要的作用。TGF-β通过经典和非经典的这两类信号转导途径来改变细胞的表型,发挥着肿瘤抑制或肿瘤促进的作用。TGF-β通过诱导上皮-间充质细胞转化(Epithelial-mesenchymal transition,EMT)来驱动肿瘤细胞进程,同时在这个过程中上皮细胞获得新的间充质的表型,使肿瘤细胞的转移能力和侵袭能力增强。这证明了TGF-β通路是促进肿瘤发展的因素。然而也有相反的证据表明,癌细胞中TGF-β信号转导途径的缺失与阻断也可以导致肿瘤细胞转移能力的增强。这篇综述回顾TGF-β对肿瘤微环境组成部分的调节和这种调节如何引起肿瘤进展作相关研究。

关键词: 转化生长因子β, 肿瘤, 微环境, 信号转导通路

Abstract: The transforming growth factor-β(TGF-β)pathway has been established as essential for cancer progression,because of its prominent role in the regulation of cell growth,differentiation and migration.Through the canonical and non-canonical arms of the signaling pathway,TGF-β instigates cellular phenotypical changes that mediate its role as both tumour suppressor and tumour promoter.TGF-β acts as a potent driver of cancer progression through the induction of epithelial-mesenchymal transition(EMT),in which epithelial cells acquire mesenchymal phenotype,leading to enhanced motility and invasion.It is evidence of the TGF-β pathway being tumour suppressive.However,there is also evidence to the contrary,abrogation of TGF-β signalling in carcinoma cells can also result in increased metastasis.This review addresses the experiments about role of an essential signalling pathway,that of transforming growth factor-β,in the regulation of components of the tumour microenvironment and research of how this contributes to tumour progression.

Key words: Transforming growth factor-β, Tumor, Microenvironment, Signalling pathway

中图分类号:

R73-37

刘本鲲综述, 徐世东, 孙大为审校. TGF-β在肿瘤微环境中多重作用的研究进展[J]. 实用肿瘤学杂志, 2015, 29(5): 454-457.

LIU Benkun, XU Shidong, SUN Dawei. The progress on roles of TGF-β in tumour microenvironment[J]. PRACTICAL ONCOLOGY JOURNAL, 2015, 29(5): 454-457.

参考文献

1 Hawinkels L,Paauwe M,Verspaget HW,et al.Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts[J].Oncogene,2014,33(1):97-107.
2 Padua D,Massagué J.Roles of TGF-β in metastasis[J].Cell Res,2009,19(1):89-102.
3 Massague J.TGF-β signalling in context[J].Nature Rev Mol Cell Biol,2012,13(10):616-630.
4 Davis BN,Hilyard AC,Nguyen PH,et al.Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha[J].Mol Cell,2010,39(3):373-384.
5 Pten Dijke P,Hill CS.New insights into TGF-β-Smad signalling[J].Trends Biochem Sci,2004,29(5):265-273.
6 吴涛,邹小明,宋茂力,等.TGF-βⅡ 型受体,Smad4 与 Smad7 蛋白在胃癌中的表达[J].实用肿瘤学杂志,2008,21(6):513-515.
7 Ewen ME,Oliver CJ,Sluss HK,et al.p53-dependent repression of CDK4 translation in TGF-beta-induced G1 cell-cycle arrest[J].Gene Dev,1995,9(2):204-217.
8 Shi J,Zhuang Y,Liu XK,et al.TGF-beta induced RBL2 expression in renal cancer cells by down-regulating miR-93[J].Clin Transl Oncol,2014,16(11):986-992.
9 Tian M,Neil JR,Schiemann WP.Transforming growth factor-β and the hallmarks of cancer[J].Cell Signal,2011,23(6):951-962.
10 Polyak K,Weinberg RA.Transitions between epithelial and mesenchymal states:acquisition of malignant and stem cell traits[J].Nat Rev Cancer,2009,9(4):265-273.
11 Giampieri S,Manning C,Hooper S,et al.Localized and reversible TGF-β signalling switches breast cancer cells from cohesive to single cell motility[J].Nat Cell Biol,2009,11(11):1287-1296.
12 Massague J.TGF-β in Cancer[J].Cell,2008,134(2):215-230.
13 Mima K,Hayashi H,Kuroki H,et al.Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma:Clinical significance of transforming growth factor-β signaling[J].Oncol Lett,2013,5(1):149-154.
14 Bierie B,Chung CH,Parker JS,et al.Abrogation of TGF-β signaling enhances chemokine production and correlates with prognosis in human breast cancer[J].J Clin Invest,2009,119(6):1571-1582.
15 Hawinkels L,Paauwe M,Verspaget HW,et al.Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts[J].Oncogene,2014,33(1):97-107.
16 Ungefroren H,Sebens S,Groth S,et al.Differential roles of Src in transforming growth factor-β regulation of growth arrest,epithelial-to-mesenchymal transition and cell migration in pancreatic ductal adenocarcinoma cells[J].Int J Oncol,2011,38(3):797-805.
17 姜永冬,陈艳波,何川,等.hCLP46 基因在不同侵袭转移潜能乳腺癌细胞表达中的差异及其意义[J].实用肿瘤学杂志,2012,26(4):336-339.
18 Cédric C,Factor VM,Thorgeirsson SS.Transforming growth factor-beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer[J].Hepatology,2008,47(6):2059-2067.
19 Paiva CE,Serrano SV,Paiva BSR,et al.Absence of TGF-βRII predicts bone and lung metastasis and is associated with poor prognosis in stage III breast tumors[J].Cancer Biomark,2012,11(5):209-217.
20 Malkoski SP,Haeger SM,Cleaver TG,et al.Loss of transforming growth factor beta type II receptor increases aggressive tumor behavior and reduces survival in lung adenocarcinoma and squamous cell carcinoma[J].Clin Cancer Res,2012,18(8):2173-2183.
21 Korpal M,Kang Y.Targeting the transforming growth factor-β signalling pathway in metastatic cancer[J].Eur J Cancer,2010,46(7):1232-1240.
22 Yang L,Huang J,Ren X,et al.Abrogation of TGF-β signaling in mammary carcinomas recruits Gr-1+ CD11b+ myeloid cells that promote metastasis[J].Cancer Cell,2008,13(1):23-35.
23 Ijichi H,Chytil A,Gorska AE,et al.Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma[J].J Clin Invest,2011,121(10):4106-4117.
24 Kato M,Putta S,Wang M,et al.TGF-β activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN[J].Nat Cell Biol,2009,11(7):881-889.
25 Malkoski SP,Haeger SM,Cleaver TG,et al.Loss of transforming growth factor beta type II receptor increases aggressive tumor behavior and reduces survival in lung adenocarcinoma and squamous cell carcinoma[J].Clin Cancer Res,2012,18(8):2173-2183.
26 Yang P,Li QJ,Feng Y,et al.TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma[J].Cancer Cell,2012,22(3):291-303.
27 Wang J,Wang Y,Ma Y,et al.Transforming growth factor β-regulated microRNA-29a promotes angiogenesis through targeting the phosphatase and tensin homolog in endothelium[J].J Biol Chem,2013,288(3):10418-10426.

[1]	孙力超,杨婧,孙立新,张媛,杨治华,冉宇靓. 采用肝癌球体细胞筛选鉴定识别肝癌干细胞的单抗[J]. 实用肿瘤学杂志, 2019, 33(3): 193-199.
[2]	张佳文,于雁,张薇,曹京燕,罗雯,尚利华. 基于UPLC-TOF/MS的小细胞肺癌患者血清代谢组学研究[J]. 实用肿瘤学杂志, 2019, 33(3): 200-205.
[3]	孙立春,李丹丹,李净,于凤玲. CCDC8和TGF-β1在非小细胞肺癌中的表达及临床意义[J]. 实用肿瘤学杂志, 2019, 33(3): 215-221.
[4]	张茂祥,孙惠昕,宋冰冰. 2008—2012年哈尔滨市道里区恶性肿瘤发病与死亡分析[J]. 实用肿瘤学杂志, 2019, 33(3): 261-265.
[5]	刘乙澍,曲国蕃. 长链非编码RNA在骨肉瘤中的研究进展[J]. 实用肿瘤学杂志, 2019, 33(3): 266-270.
[6]	侯玉雪,李晓莉. Wnt7a与恶性肿瘤的关系及研究进展[J]. 实用肿瘤学杂志, 2019, 33(3): 271-275.
[7]	朱琳,张春霞. 纳米载药系统靶向肿瘤干细胞的研究进展[J]. 实用肿瘤学杂志, 2019, 33(3): 276-279.
[8]	徐晖, 李希, 周春水. 应用以人转录组为靶点的shRNA文库筛选肺癌肿瘤相关抑制基因[J]. 实用肿瘤学杂志, 2019, 33(2): 97-102.
[9]	李诚, 兰莉, 杨超, 张婷婷, 王蕊, 林琳, 田文静. 2015—2017年哈尔滨市恶性肿瘤发病与死亡特征分析[J]. 实用肿瘤学杂志, 2019, 33(1): 62-66.
[10]	丁界先, 张津, 陈永刚, 王兴文综述, 王栓科审校. Wnt信号通路与肿瘤发生的研究进展[J]. 实用肿瘤学杂志, 2019, 33(1): 73-77.
[11]	于芳, 赵培. TRAP1在食管癌发展中的作用及机制研究[J]. 实用肿瘤学杂志, 2018, 32(6): 515-519.
[12]	王亚龙, 吕章艳, 张帆, 冯小双, 魏锣沛, 李鑫, 温艳, 高禹舜, 薛奇, 高树庚, 谭锋维. 人乳头状瘤病毒感染与肺癌预后相关性的Meta分析[J]. 实用肿瘤学杂志, 2018, 32(6): 520-526.
[13]	付艳丽, 余杨, 卫玮, 邹晶晶, 孙翔. 高危型人乳头状瘤病毒载量和Th1/Th2不均衡表达预测宫颈癌变进程的研究[J]. 实用肿瘤学杂志, 2018, 32(6): 533-537.
[14]	唐淑丽, 何匡邦, 张纯慧, 程佳楠, 张艳桥. 胃癌组织中miR-320a和CYLD的表达及与临床病理特征及预后的关系[J]. 实用肿瘤学杂志, 2018, 32(6): 538-544.
[15]	阚钧, 周岱翰综述, 张恩欣审校. 肿瘤合并心血管疾病的研究进展[J]. 实用肿瘤学杂志, 2018, 32(6): 558-561.