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中华细胞与干细胞杂志(电子版) ›› 2019, Vol. 09 ›› Issue (03) : 182 -187. doi: 10.3877/cma.j.issn.2095-1221.2019.03.009

所属专题: 文献

综述

CD109的生物学功能及其与乳腺癌的关系
张亚男1, 宋娜2, 徐丽2, 张学东2, 韩冬3, 李荣贵4, 韩发彬1,()   
  1. 1. 266071 青岛大学生命科学学院;252000 聊城,山东聊城大学/聊城市人民医院组织工程与再生医学研究所
    2. 252000 聊城,山东聊城大学/聊城市人民医院组织工程与再生医学研究所
    3. 250101 济南,山东美加赛培生物科技有限公司
    4. 266071 青岛大学生命科学学院
  • 收稿日期:2019-01-21 出版日期:2019-06-01
  • 通信作者: 韩发彬
  • 基金资助:
    山东省自然科学基金(ZR2019PC017)

Biological function of CD109 and its relationship with breast cancer

Ya'nan Zhang1, Na Song2, Li Xu2, Xuedong Zhang2, Dong Han3, Ronggui Li4, Fabin Han1,()   

  1. 1. College of Life Sciences, Qingdao University, Qingdao 266071, China; The Institute for Tissue Engineering and Regenerative, Liaocheng University/Liaocheng People's Hospital, Liaocheng 252000, China
    2. The Institute for Tissue Engineering and Regenerative, Liaocheng University/Liaocheng People's Hospital, Liaocheng 252000, China
    3. Shandong Meijia Sai Pei Biotechnology Co., Ltd. Jinan 250101, China
    4. College of Life Sciences, Qingdao University, Qingdao 266071, China
  • Received:2019-01-21 Published:2019-06-01
  • Corresponding author: Fabin Han
  • About author:
    Corresponding author: Han Fabin, Email:
引用本文:

张亚男, 宋娜, 徐丽, 张学东, 韩冬, 李荣贵, 韩发彬. CD109的生物学功能及其与乳腺癌的关系[J/OL]. 中华细胞与干细胞杂志(电子版), 2019, 09(03): 182-187.

Ya'nan Zhang, Na Song, Li Xu, Xuedong Zhang, Dong Han, Ronggui Li, Fabin Han. Biological function of CD109 and its relationship with breast cancer[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2019, 09(03): 182-187.

CD109是细胞的一种表面抗原,通过TGF-β信号通路传导来调控细胞的增殖与分化,CD109还同时参与JAK-STAT和表皮生长因子受体(EGFR)信号通路调节细胞增殖与分化功能,与一些疾病及肿瘤的发生与发展密切相关。近年来研究发现CD109在基底细胞样乳腺癌中呈明显高表达,并且与基底细胞样乳腺癌易复发及转移相关,导致治疗和预后效果差。因此CD109检测分析对乳腺癌的诊断及治疗具有重要意义,CD109与乳腺癌的关系成为当前研究的热点。本文综述了CD109的生物学功能及CD109与乳腺癌的关系。

CD109 is a cell surface antigen that regulates cell proliferation and differentiation by negatively regulating TGF-β signaling pathway. It also participates in JAK-STAT and EGFR signaling pathways to regulate cell functions of proliferation and differentiation. It is closely related to the occurrence and development of some diseases and malignant tumors. In recent years, the CD109 has been found to be highly expressed in basal-like breast cancer. The treatment is not satisfying because of the recurrence and metastasis of the basal-like breast cancer. Thus the detection and analysis of CD109 on tumors is very important for the diagnosis and treatment of breast cancer, and the relationship between CD109 and breast cancer has become a hot topic of current research. This review focuses on the biological functions of CD109 and the relationship between CD109 and breast cancer.

图1 CD109影响细胞增殖和分化的作用信号通路
图2 CD109影响某些疾病发生的信号通路
图3 CD109影响细胞迁移和侵袭的信号通路
表1 乳腺癌的分子病理分型及标志物
[1]
Schuh AC,Watkins NA,Nguyen Q, et al. A tyrosine703serine polymorphism of CD109 defines the Gov platelet alloantigens[J]. Blood, 2002, 99(5):1692-1698.
[2]
Finnson KW,Tam BY,Liu K, et al. Identification of CD109 as part of the TGF-beta receptor system in human keratinocytes[J]. FASEB J, 2006, 20(9):1525-1527.
[3]
Shiraki Y,Mii S,Enomoto A, et al. Significance of perivascular tumour cells defined by CD109 expression in progression of glioma[J]. J Pathol, 2017, 243(4):468-480.
[4]
Sato T,Murakumo Y,Hagiwara S, et al. High-level expression of CD109 is frequently detected in lung squamous cell carcinomas[J]. Pathol Int, 2007, 57(11):719-724.
[5]
Giesert C,Marxer A,Sutherland DR, et al. Antibody W7C5 defines a CD109 epitope expressed on CD34+ and CD34- hematopoietic and mesenchymal stem cell subsets[J]. Ann N Y Acad Sci, 2010, 996(1):227-230.
[6]
Murray LJ,Bruno E,Uchida N, et al. CD109 is expressed on a subpopulation of CD34(+) cells enriched in hematopoietic stem and progenitor cells[J]. Exp Hematol, 1999, 27(8):1282-1294.
[7]
Rappold I,Ziegler BL,Köhler I, et al. Functional and phenotypic characterization of cord blood and bone marrow subsets expressing FLT3 (CD135) receptor tyrosine kinase[J]. Blood, 1997, 90:111-125.
[8]
Li J,Xin JJ,Zhang LY, et al. Human hepatic progenitor cells Express hematopoietic cell markers CD45 and CD109[J]. Int J Med Sci, 2014, 11(1):65-79.
[9]
Ertel K,Al-Tawil M,Santoso S, et al. Relevance of the HPA-15(gov)polymorphism on CD109 in alloimmune thrombocytopenic syndromes [J]. Transfusion, 2005, 45(3):366-373.
[10]
Hasegawa M,Hagiwara S,Sato T, et al. CD109, a new marker for myoepithelial cells of mammary,salivary,and lacrimal glands and prostate basal cells[J]. Pathol Int, 2007, 57(5):245-250.
[11]
Sutherland DR,Yeo E,Ryan A, et al. Identification of a cell-surface antigen associated with activated T lymphoblasts and activated platelets [J]. Blood, 1991, 77(1):84-93.
[12]
Solomon KR,Sharma P,Chan M, et al. CD109 represents a novel branch of the alpha 2-macroglobulin/complement gene family[J]. Gene, 2004, 327(2):171-183.
[13]
Hashimoto M, Ichihara M, Watanabe T, et al. Expression of CD109 in human cancer[J]. Oncogene, 2004, 23(20):3716-3720.
[14]
Mokrosiński J,Krajewska WM. TGF beta signalling accessory receptors[J]. Postepy Biochem, 2008, 54(3): 264-273.
[15]
Bernabeu C,Lopez-Novoa JM,Quintanilla M. The emerging role of TGF-beta superfamily coreceptors in cancer[J]. Biochim Biophys Acta, 2009, 1792(10):954-973.
[16]
Li C,Hancock MA,Sehgal P, et al. Soluble CD109 binds TGF-beta and antagonizes TGF-beta signalling and responses[J]. Biochem J, 2016, 473(5):537-547.
[17]
Bizet AA,Liu K,Tran-Khanh N, et al. The TGF-β co-receptor, CD109, promotes internalization and degradation of TGF-β receptors[J]. Biochim Biophys Acta, 2011, 1813(5):742-753.
[18]
Bizet AA,Tran-Khanh N,Saksena A, et al. CD109-mediated degradation of TGF-β receptors and inhibition of TGF-β responses involve regulation of SMAD7 and Smurf2 localization and function[J]. J Cell Biochem, 2012, 113(1):238-246.
[19]
Tsai YL,Ha DP,Zhao H, et al. Endoplasmic reticulum stress activates SRC, relocating chaperones to the cell surface where GRP78/CD109 blocks TGF-beta signaling[J]. Proc Natl Acad Sci U S A, 2018, 115(18):E4245-E4254.
[20]
Winocour S,Vorstenbosch J,Trzeciak AA, et al. CD109, a novel TGF-beta antagonist, decreases fibrotic responses in a hypoxic wound model [J]. Exp Dermatol, 2014, 23(7):475-479.
[21]
Vorstenbosch J,Gallant-Behm C,Trzeciak A, et al. Transgenic mice overexpressing CD109 in the epidermis display decreased inflammation and granulation tissue and improved collagen architecture during wound healing[J]. Wound Repair Regen, 2013, 21(2):235-246.
[22]
Yokoyama M,Ichinoe M,Okina S, et al. CD109, a negative regulator of TGF-β signaling, is a putative risk marker in diffuse large B-cell lymphoma[J]. Int J Hematol, 2017, 105(5):614-622.
[23]
Zong GJ,Xu ZW,Zhang SS, et al. CD109 mediates cell survival in hepatocellular carcinoma cells[J]. Dig Dis Sci, 2016, 61(8):2303-2314.
[24]
Levy DE,Darnell JE. STATs: transcriptional control and biological impact[J]. Nat Rev Mol Cell Biol, 2002, 3(9):651-662.
[25]
Shinagawa K,Yanamoto S,Naruse T, et al. Clinical roles of interleukin-6 and STAT3 in oral squamous cell carcinoma[J]. Pathol Oncol Res, 2017, 23(2):425-431.
[26]
Kusaba T,Nakayama T,Yamazumi K, et al. Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma;correlation with clinicopathological factors[J]. J Clin Pathol, 2005, 58(8):833-838.
[27]
Litvinov IV,Bizet AA,Binamer Y, et al. CD109 release from the cell surface in human keratinocytes regulates TGF-beta receptor expression, TGF-beta signalling and STAT3 activation: relevance to psoriasis[J]. Exp Dermatol, 2011, 20(8):627-632.
[28]
Mii S,Murakumo Y,Asai N, et al. Epidermal hyperplasia and appendage abnormalities in mice lacking CD109[J]. Am J Pathol, 2012, 181(4):1180-1189.
[29]
Chuang CH,Greenside PG,Rogers ZN, et al. Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis[J]. Nat Med, 2017, 23(3):291-300.
[30]
Singh D,Attri BK,Gill RK, et al. Review on EGFR inhibitors: critical updates[J]. Mini Rev Med Chem, 2016, 16(14):1134-1166.
[31]
Jedlinski A,Garvin S,Johansson AC, et al. Cetuximab sensitivity of head and neck squamous cell carcinoma xenografts is associated with treatment-induced reduction in EGFR, pEGFR, and pSrc[J]. J Oral Pathol Med, 2016, 46(9):717-724.
[32]
Joshi A,Zanwar S,Noronha V, et al. EGFR mutation in squamous cell carcinoma of the lung: does it carry the same connotation as in adenocarcinomas?[J]. Onco Targets Ther, 2017, 10:1859-1863.
[33]
Gonzales CB,De LA Chapa JJ,Saikumar P, et al. Co-targeting ALK and EGFR parallel signaling in oral squamous cell carcinoma[J]. Oral Oncol, 2016, 59:12-19.
[34]
Zhang JM,Hashimoto M,Kawai K, et al. CD109 expression in squamous cell carcinoma of the uterine cervix[J]. Pathol Int, 2005, 55(4):165-169.
[35]
Hagiwara S,Murakumo Y,Sato T, et al. Up-regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity[J]. Cancer Sci, 2008, 99(10):1916-1923.
[36]
Dong F,Liu F,Yan S, et al. Elevated expression of CD109 in esophageal squamous cell carcinoma[J]. Pathol Oncol Res, 2015, 21(4):1273-1275.
[37]
Dong FY,Wang J,Xu YH, et al. CD109 expression is upregulated in penile squamous cell carcinoma[J]. Oncol Lett, 2017, 14(5):6012-6016.
[38]
Zhang JM,Murakumo Y,Hagiwara S, et al. CD109 attenuates TGF-beta 1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells[J]. Biochem Biophys Res Commun, 2015, 459(2):252-258.
[39]
Perou CM,Sorlie T,Eisen MB, et al. Molecular portraits of human breast tumours[J]. Nature, 2000, 406(6797):747-752.
[40]
Sorlie T,Tibshirani R,Parker J, et al. Repeated observation of breast tumor subtypes in Independent gene expression data sets[J]. Proc Natl Acad Sci U S A, 2003, 100(14):8418-8423.
[41]
Bertucci F,Finetti P,Birnbaum D. Basal breast cancer:a complex and deadly molecular subtype[J]. Curr Mol Med, 2012, 12(1):96-110.
[42]
Hasegawa M,Moritani S,Murakumo Y, et al. CD109 expression in basal-like breast carcinoma[J]. Pathol Int, 2008, 58(5):288-294.
[43]
侍朋举,赵燕会,蔡海峰, 等. CD109在基底细胞样乳腺癌中的表达及意义[J]. 实用肿瘤杂志, 2012, 27(6):613-616.
[44]
侍朋举,蔡海峰,牛凤玲, 等. CD109、HMW-CK、Vimentin、p63和AR在基底细胞样乳腺癌中的表达及其临床意义[J]. 临床肿瘤学杂志, 2012, 17(10):884-888.
[45]
Tao J,Li HB,Li QW, et al. CD109 is a potential target for triple-negative breast cancer[J]. Tumour Biol, 2014, 35(12):12083-12090.
[46]
Hockla A,Radisky DC,Radisky ES. Mesotrypsin promotes malignant growth of breast cancer cells through shedding of CD109[J]. Breast Cancer Res Treat, 2010, 124(1):27-38.
[47]
Chen C,Duan J,Shen A, et al. Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease[J]. Journal of Neurorestoratology, 2016, 4:23-33.
[48]
Sunagawa M,Mii S,Enomoto A, et al. Suppression of skin tumorigenesis in CD109-deficient mice[J]. Oncotarget, 2016, 7(50): 82836-82850.
[49]
Liu XX,Feng AP,He YM, et al. Association of down-regulation of CD109 expression with up-expression of Smad7 in pathogenesis of psoriasis[J]. J Huazhong Univ Sci Technolog Med Sci, 2016, 36(1):132-136.
[50]
Zhou S,Cecere R,Philip A, CD109 released from human bone marrow mesenchymal stem cells attenuates TGF-β-induced epithelial to mesenchymal transition and stemness of squamous cell carcinoma[J]. Oncotarget, 2017, 8(56):95632-95647.
[51]
Vorstenbosch J,Nguyen CM,Zhou SA, et al. Overexpression of CD109 in the epidermis differentially regulates ALK1 versus ALK5 signaling and modulates extracellular matrix synthesis in the skin[J]. J Invest Dermatol, 2017, 137(3):641-649.
[52]
Zhao YY,Ma J,Fan YL, et al. TGF-beta transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways[J]. Mol Oncol, 2018, 12(3):305-321.
[53]
Zhang LY,Fu ZL,Li X, et al. Transforming growth factor -activated kinase 1 inhibitor suppresses the proliferation in triple-negative breast cancer through TGF-/TGFR pathway[J]. Chem Biol Drug Des, 2017, 90(3):450-455.
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