切换至 "中华医学电子期刊资源库"

中华妇幼临床医学杂志(电子版) ›› 2016, Vol. 12 ›› Issue (03) : 349 -353. doi: 10.3877/cma.j.issn.1673-5250.2016.03.018

所属专题: 文献

综述

Smad4与女性生殖系统恶性肿瘤关系的研究进展
陈海燕1, 郝敏1   
  1. 1. 030001 太原,山西医科大学第二医院妇产科
  • 收稿日期:2016-02-28 修回日期:2016-05-14 出版日期:2016-06-01

Research progress of relations between Smad4 and malignant tumor of female reproductive system

Haiyan Chen1, Min Hao1   

  1. 1. Department of Gynaecology and Obstetrics, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2016-02-28 Revised:2016-05-14 Published:2016-06-01
  • About author:
    Corresponding author: Wang Zhilian, Email:
引用本文:

陈海燕, 郝敏. Smad4与女性生殖系统恶性肿瘤关系的研究进展[J]. 中华妇幼临床医学杂志(电子版), 2016, 12(03): 349-353.

Haiyan Chen, Min Hao. Research progress of relations between Smad4 and malignant tumor of female reproductive system[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2016, 12(03): 349-353.

Smad4作为转化生长因子(TGF)-β信号通路中的细胞内信使,越来越受到关注。众多研究发现,Smad4在女性生殖系统恶性肿瘤中起着抑癌基因的作用。Smad4蛋白在肿瘤中表达降低或缺失,可促进肿瘤发生、发展。Smad4与女性生殖系统恶性肿瘤患者的低生存率及不良预后关系密切。随着研究的深入,Smad4有望成为女性生殖系统恶性肿瘤有价值的诊断与预后评估标志物,以及治疗靶点。笔者拟就Smad4与女性生殖系统恶性肿瘤关系的研究进展进行综述如下。

Smad4, one of the intracellular messengers of transforming growth factor (TGF)-β signaling pathway, has been paid more and more attention. Lots of studies have proved that Smad4 plays the role of tumor suppressor gene in malignant tumor of female reproductive system. The reduced or deleted expression of Smad4 protein in those tumor tissues can promote the occurence and development of carcinoma. Smad4 is also associated with low survival and poor prognosis of patients with malignant tumor of female reproductive system. With further research, Smad4 may be a valuable marker of diagnosis and evaluation of the prognosis and target of malignancy treatment in malignant tumor of female reproductive system. This review will summarize the research progress of relations between Smad4 and malignant tumor of female reproductive system.

1
Waite KA, Eng C. From developmental disorder to heritable cancer:it's all in the BMP/TGF-beta family[J]. Nat Rev Genet, 2003, 4(10):763-773.
2
Ikushima H, Miyazono K. TGFbeta signalling:a complex web in cancer progression[J]. Nat Rev Cancer, 2010, 10(6):415-424.
3
Massague J. TGFbeta in cancer[J]. Cell, 2008, 134(2):215-230.
4
Tang B, Vu M, Booker T, et al. TGF-beta switches from tumor suppressor to prometastatic factor in a model of breast cancer progression[J]. J Clin Invest, 2003, 112(7):1116-1124.
5
Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression[J]. Nat Genet, 2001, 29(2):117-129.
6
Moustakas A, Souchelnytskyi S, Heldin CH. Smad regulation in TGF-beta signal transduction[J]. J Cell Sci, 2001, 114(Pt 24):4359-4369.
7
Heldin CH, Moustakas A. Role of Smads in TGFbeta signaling[J]. Cell Tissue Res, 2012, 347(1):21-36.
8
Shi Y, Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus[J]. Cell, 2003, 113(6):685-700.
9
Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling[J]. Nature, 2003, 425(6958):577-584.
10
Yang G, Yang X. Smad4-mediated TGF-beta signaling in tumorigenesis[J]. Int J Biol Sci, 2010, 6(1):1-8.
11
Hahn SA, Schutte M, Hoque AT, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1[J]. Science, 1996, 271(5247):350-353.
12
Zhang Y, Musci T, Derynck R. The tumor suppressor Smad4/DPC 4 as a central mediator of Smad function[J]. Curr Biol, 1997, 7(4):270-276.
13
Joshi A, Cao D. TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly effect[J]. Front Biosci (Landmark Ed), 2010, 15:180-194.
14
Horie K, Yamashita H, Mogi A, et al. Lack of transforming growth factor-beta type Ⅱ receptor expression in human retinoblastoma cells[J]. J Cell Physiol, 1998, 175(3):305-313.
15
Arrick BA, Korc M, Derynck R. Differential regulation of expression of three transforming growth factor beta species in human breast cancer cell lines by estradiol[J]. Cancer Res, 1990, 50(2):299-303.
16
Jeng MH, ten Dijke P, Iwata KK, et al. Regulation of the levels of three transforming growth factor beta mRNAs by estrogen and their effects on the proliferation of human breast cancer cells[J]. Mol Cell Endocrinol, 1993, 97(1-2):115-123.
17
Jakob J, Nagase S, Gazdar A, et al. Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line[J]. Genes Chromosomes Cancer, 2005, 42(4):372-383.
18
Zhong D, Morikawa A, Guo L, et al. Homozygous deletion of SMAD4 in breast cancer cell lines and invasive ductal carcinomas[J]. Cancer Biol Ther, 2006, 5(6):601-607.
19
Ren Y, Wu L, Frost AR, et al. Dual effects of TGF-beta on ERalpha-mediated estrogenic transcriptional activity in breast cancer[J]. Mol Cancer, 2009, 8:111.
20
Wu L, Wu Y, Gathings B, et al. Smad4 as a transcription corepressor for estrogen receptor alpha[J]. J Biol Chem, 2003, 278(17):15192-151200.
21
Li W, Qiao W, Chen L, et al. Squamous cell carcinoma and mammary abscess formation through squamous metaplasia in Smad4/Dpc4 conditional knockout mice[J]. Development, 2010, 130(24):6143-6153.
22
Giampieri S, Manning C, Hooper S, et al. Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility[J]. Nat Cell Biol, 2009, 11(11):1287-1296.
23
Mi Z, Guo H, Wai PY, et al. Differential osteopontin expression in phenotypically distinct subclones of murine breast cancer cells mediates metastatic behavior[J]. J Biol Chem, 2004, 279(45):46659-46667.
24
Kassem L, Deygas M, Fattet L, et al. TIF1γ interferes with TGFβ1/SMAD4 signaling to promote poor outcome in operable breast cancer patients[J]. BMC Cancer, 2015, 15:453.
25
Xie W, Mertens JC, Reiss DJ, et al. Alterations of Smad signaling in human breast carcinoma are associated with poor outcome: a tissue microarray study[J]. Cancer Res, 2002, 62(2):497-505.
26
de Kruijf EM, Dekker TJ, Hawinkels LJ, et al. The prognostic role of TGF-β signaling pathway in breast cancer patients[J]. Ann Oncol, 2013, 24(2):384-390.
27
Maliekal TT, Antony ML, Nair A, et al. Loss of expression, and mutations of Smad 2 and Smad 4 in human cervical cancer[J]. Oncogene, 2003, 22(31):4889-4897.
28
Prates J, Franco-Salla GB, Dinarte Dos Santos AR, et al. ANXA1Ac2-26 peptide reduces ID1 expression in cervical carcinoma cultures[J]. Gene, 2015, 570(2):248-254.
29
Braun L, Düst M, Mikumo R, et al. Differential response of nontumorigenic and tumorigenic human papillomavirus type 16-positive epithelial cells to transforming growth factor beta 1[J]. Cancer Res, 1990, 50(22):7324-32.
30
Lee S, Cho YS, Shim C, et al. Aberrant expression of smad4 results in resistance against the growth-inhibitory effect of transforming growth factor-beta in the SiHa human cervical carcinoma cell line[J]. Int J Cancer, 2001, 94(4):500-557.
31
Baldus SE, Schwarz E, Lohrey C, et al. Smad4 deficiency in cervical carcinoma cells[J]. Oncogene, 2005, 24(5):810-819.
32
Xu Q, Wang S, Xi L, et al. Effects of human papillomavirus type 16 E7 protein on the growth of cervical carcinoma cells and immuno-escape through the TGF-beta1 signaling pathway[J]. Gynecol Oncol, 2006, 101(1):132-139.
33
Maliekal TT, Antony ML, Nair A, et al. Loss of expression, and mutations of Smad2 and Smad4 in human cervical cancer[J]. Oncogene, 2003, 22(31):4889-4897.
34
Kloth JN, Kenter GG, Spijker HS, et al. Expression of Smad2 and Smad4 in cervical cancer: absent nuclear Smad4 expression correlates with poorsurvival[J]. Mod Pathol, 2008, 21(7):866-875.
35
Mhawech-Fauceglia P, Kesterson J, Wang D, et al. Expression and clinical significance of the transforming growth factor-β signalling pathway in endometrial cancer[J]. Histopathology, 2011, 59(1):63-72.
36
Piestrzeniewicz-Ulanska D, Brys M, Semczuk A, et al. TGF-beta signaling is disrupted in endometrioid-type endometrial carcinomas[J]. Gynecol Oncol, 2004, 95(1):173-1780.
37
Zhang S, Balch C, Chan MW, et al. Identification and characterization of ovarian cancer-initiating cells from primary human tumors[J]. Cancer Res, 2008, 68(11):4311-4320.
38
Yeh KT, Chen TH, Yang HW, et al. Aberrant TGFβ/SMAD4 signaling contributes to epigenetic silencing of a putative tumor suppressor, RunX1T1 in ovarian cancer[J]. Epigenetics, 2011, 6(6):727-739.
39
Fu G, Peng C. Nodal enhances the activity of FoxO3a and its synergistic interaction with Smads to regulate cyclin G2 transcription in ovarian cancer cells[J]. Oncogene, 2011, 30(37):3953-3966.
40
Yamada SD, Baldwin RL, Karlan BY. Ovarian carcinoma cell cultures are resistant to TGF-beta1-mediated growth inhibition despite expression of functional receptors[J]. Gynecol Oncol, 1999, 75(1):72-77.
41
Baldwin RL, Tran H, Karlan BY. Loss of c-myc repression coincides with ovarian cancer resistance to transforming growth factor beta growth arrest independent of transforming growth factor beta/Smad signaling[J]. Cancer Res, 2003, 63(6):1413-1419.
42
Zhao R, Cui T, Han C, et al. DDB2 modulates TGF-β signal transduction in human ovarian cancer cells by downregulating NEDD4L[J]. Nucleic Acids Res, 2015, 43(16):7838-7849.
43
Chan MW, Huang YW, Hartman-Frey C, et al. Aberrant transforming growth factor beta1 signaling and SMAD4 nuclear translocation confer epigenetic repression of ADAM19 in ovarian cancer[J]. Neoplasia, 2008, 10(9):908-919.
44
Scharpfenecker M, van Dinther M, Liu Z, et al. BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis[J]. J Cell Sci, 2007, 120(6):964-972.
45
David L, Mallet C, Mazerbourg S, et al. Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells[J]. Blood, 2007, 109(5):1953-1961.
46
Brown MA, Zhao Q, Baker KA, et al. Crystal structure of BMP-9 and functional interactions with pro-region and receptors[J]. J Biol Chem, 2005, 280(26):25111-25118.
47
Chen C, Grzegorzewski KJ, Barash S, et al. An integrated functional genomics screening program reveals a role for BMP-9 in glucose homeostasis[J]. Nat Biotechnol, 2003, 21(3):294-301.
48
Song JJ, Celeste AJ, Kong FM, et al. Bone morphogenetic protein-9 binds to liver cells and stimulates proliferation[J]. Endocrinology, 1995, 136(10):4293-4297.
49
Herrera B, van Dinther M, Ten Dijke P, et al. Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation[J]. Cancer Res, 2009, 69(24):9254-9262.
50
Mackenzie R, Kommoss S, Winterhoff BJ, et al. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms[J]. BMC Cancer, 2015, 15:415.
51
乔友林,赵宇倩.宫颈癌的流行病学现状和预防[J/CD].中华妇幼临床医学杂志:电子版,2015,11(2):141-147.
52
李雪,孔为民,韩超,等.首都医科大学附属北京妇产医院1992-2011年间宫颈癌发病趋势分析[J/CD].中华妇幼临床医学杂志:电子版,2013,9(3):310-314.
53
Qiao P, Li G, Bi W, et al. microRNA-34a inhibits epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway[J]. BMC Cancer, 2015, 15:469.
54
Oshima M, Okano K, Muraki S, et al. Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer[J]. Ann Surg, 2013, 258(2):336-346.
55
Taniguchi C, Maitra A. It's a SMAD/SMAD world[J]. Cell, 2015, 161(6):1245-1246.
56
Yamada S, Fujii T, Shimoyama Y, et al. SMAD4 expression predicts local spread and treatment failure in resected pancreatic cancer[J]. Pancreas, 2015, 44(4):660-664.
57
Xie W, Mertens JC, Reiss DJ, et al. Alterations of Smad signaling in human breast carcinoma are associated with poor outcome: a tissue microarray study[J]. Cancer Res, 2002, 62(2):497-505.
58
Liu NN, Xi Y, Callaghan MU, et al. SMAD4 is a potential prognostic marker in human breast carcinomas[J]. Tumour Biol, 2014, 35(1):641-650.
59
Isaksson-Mettävainio M, Palmqvist R, Dahlin AM, et al. High SMAD4 levels appear in microsatellite instability and hypermethylated colon cancers, and indicate a better prognosis[J]. Int J Cancer, 2012, 131(4):779-788.
60
Alazzouzi H, Alhopuro P, Salovaara R, et al. SMAD4 as a prognostic marker in colorectal cancer[J]. Clin Cancer Res, 2005, 11(7):2606-2611.
61
Voorneveld PW, Jacobs RJ, Kodach LL, et al. A meta-analysis of SMAD4 immunohistochemistry as a prognostic marker in colorectal cancer[J]. Transl Oncol, 2015, 8(1):18-24.
62
Du Y, Zhou X, Huang Z, et al. Meta-analysis of the prognostic value of smad4 immunohistochemistry in various cancers[J]. PLoS One, 2014, 9(10):e110182.
[1] 韩丹, 王婷, 肖欢, 朱丽容, 陈镜宇, 唐毅. 超声造影与增强CT对儿童肝脏良恶性病变诊断价值的对比分析[J]. 中华医学超声杂志(电子版), 2023, 20(09): 939-944.
[2] 郏亚平, 曾书娥. 含鳞状细胞癌成分的乳腺化生性癌的超声与病理特征分析[J]. 中华医学超声杂志(电子版), 2023, 20(08): 844-848.
[3] 姚宏伟, 魏鹏宇, 高加勒, 张忠涛. 不断提高腹腔镜右半结肠癌D3根治术的规范化[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 1-4.
[4] 杜晓辉, 崔建新. 腹腔镜右半结肠癌D3根治术淋巴结清扫范围与策略[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 5-8.
[5] 周岩冰, 刘晓东. 腹腔镜右半结肠癌D3根治术消化道吻合重建方式的选择[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 9-13.
[6] 唐旭, 韩冰, 刘威, 陈茹星. 结直肠癌根治术后隐匿性肝转移危险因素分析及预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 16-20.
[7] 张生军, 赵阿静, 李守博, 郝祥宏, 刘敏丽. 高糖通过HGF/c-met通路促进结直肠癌侵袭和迁移的实验研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 21-24.
[8] 张焱辉, 张蛟, 朱志贤. 留置肛管在中低位直肠癌新辅助放化疗后腹腔镜TME术中的临床研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 25-28.
[9] 李凤仪, 李若凡, 高旭, 张超凡. 目标导向液体干预对老年胃肠道肿瘤患者术后血流动力学、胃肠功能恢复的影响[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 29-32.
[10] 李建美, 邓静娟, 杨倩. 两种术式联合治疗肝癌合并肝硬化门静脉高压的安全性及随访评价[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 41-44.
[11] 燕速, 霍博文, 徐惠宁. 4K荧光腹腔镜扩大右半结肠CME+D3根治术及No.206、No.204组淋巴结清扫术[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 14-14.
[12] 钱龙, 陆晓峰, 王行舟, 杜峻峰, 沈晓菲, 管文贤. 神经系统调控胃肠道肿瘤免疫应答研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 86-89.
[13] 曹长青, 郭新艳, 高源, 张存, 唐海利, 樊东, 杨小军, 张松, 赵华栋. 肿瘤微环境参与介导HER2阳性乳腺癌曲妥珠单抗耐药的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 90-95.
[14] 徐军, 姬园园, 陈君平, 王健. 伴菊形团结构的脑膜瘤合并颅骨侵犯一例并文献复习[J]. 中华临床医师杂志(电子版), 2023, 17(08): 916-919.
[15] 王军, 刘鲲鹏, 姚兰, 张华, 魏越, 索利斌, 陈骏, 苗成利, 罗成华. 腹膜后肿瘤切除术中大量输血患者的麻醉管理特点与分析[J]. 中华临床医师杂志(电子版), 2023, 17(08): 844-849.
阅读次数
全文


摘要