三叶因子3在甲状腺乳头状癌TPC-1细胞上皮间质转化中的作用及机制

林旭 王志勇 吴靖芳 张文静 张静 薛刚

解剖学报 ›› 2018, Vol. 49 ›› Issue (2) : 204-211.

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解剖学报 ›› 2018, Vol. 49 ›› Issue (2) : 204-211. DOI: 10.16098/j.issn.0529-1356.2018.02.011
肿瘤生物学

三叶因子3在甲状腺乳头状癌TPC-1细胞上皮间质转化中的作用及机制

  •  林旭1 王志勇1 吴靖芳1* 张文静1 张静1 薛刚2*
作者信息 +

Effect and mechanism of trefoil factor 3 on epithelial-mesenchymal transition of papillary thyroid carcinoma TPC-1 cells

  • LIN Xu1 WANG Zhi-yong1 WU Jing-fang 1* ZHANG Wen-jing1 ZHANG Jing1 XUE Gang 2*
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摘要

目的 探讨三叶因子3(TFF3)基因沉默对人甲状腺乳头状癌TPC-1细胞迁移、侵袭、克隆形成能力以及对上皮间质转化(EMT)的影响及机制。 方法 免疫组织化学技术检测甲状腺乳头状癌组织芯片中Snail与TFF3的表达。划痕实验、侵袭实验和克隆形成实验分别检测TFF3基因对TPC-1细胞迁移、侵袭和克隆能力的影响;实时定量聚合酶链反应(Real-time PCR)、免疫印迹法和免疫细胞化学染色检测上皮间质转化标志物及丝裂原活化蛋白激酶(MAPK)通路相关蛋白的变化。结果 31例甲状腺乳头状癌组织中,Snail蛋白于癌细胞胞质表达,31例癌旁组织阴性表达;Snail蛋白与TFF3表达呈正相关(r=0.8450,P<0.05)。TFF3基因沉默后,人TPC-1细胞的细胞迁移、侵袭和克隆形成能力均明显降低(P<0.01);TPC-1细胞上皮间质转化标志物及MAPK通路相关蛋白细胞外调节蛋白激酶(ERK)1/2和p-ERK1/2也显著降低(P<0.05)。 结论 沉默TFF3可能通过MAPK通路相关蛋白ERK1/2抑制上皮间质转化,降低TPC-1细胞迁移、侵袭和增殖能力。

Abstract

Objective To explore the roles and mechanisms of silence trefoil factor 3(TFF3) on migration, invasion,clony formation and epithelial-mesenchymal transition of thyroid papillary carcinoma TPC-1 cells. Methods Expressions of Snail and TFF3 in tissue microarrays of thyroid papillary carcinoma were analysed by immunohistochemistry. Invasion assays, wound healing assays and colony formation tests were performed to detect the effects of TFF3 on migration, invasion and clony formation of TPC-1 cells. Epithelial-mesenchymal transition(EMT) markers and regulatory molecules were detected by Real-time PCR assay,Western blotting and immunocytochemistry in TPC-1 cells and mitogen-activated protein kinase (MAPK) signalling pathway related proteins were examined by Western blotting and immunocytochemistry. Results In 31 cases of papillary thyroid carcinoma, Snail and TFF3 positive signals were observed in the cytoplasm of papillary throid carcinoma(PTC),and were negative in the para-carcinoma.The expression of Snail in papillary thyroid carcinoma showed positive correlation with the expression of TFF3 protein(r=0.8450,P<0.05). Siliencing TFF3 expression markedly inhibited the ability of migration,invasion and clony formation in vitrovia suppressing of the MAPK signalling pathway and inhibited the process of EMT(P<0.05 or P<0.01). Conclusion Knockdown of TFF3 inhibits TPC-1 cells migration,invasion clony formation and EMT related proteins epression through suppressing MAPK/ERK signalling pathway.

关键词

三叶因子3 / 上皮间质转化 / 免疫组织化学 / 免疫印迹法 / 实时定量聚合酶链反应 /

Key words

Trefoil factor 3 / Epithelial-mesenchymal transition / Immunohistochemistry / Western blotting / Real-time PCR / Human

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林旭 王志勇 吴靖芳 张文静 张静 薛刚. 三叶因子3在甲状腺乳头状癌TPC-1细胞上皮间质转化中的作用及机制[J]. 解剖学报. 2018, 49(2): 204-211 https://doi.org/10.16098/j.issn.0529-1356.2018.02.011
LIN Xu WANG Zhi-yong WU Jing-fang ZHANG Wen-jing ZHANG Jing XUE Gang. Effect and mechanism of trefoil factor 3 on epithelial-mesenchymal transition of papillary thyroid carcinoma TPC-1 cells[J]. Acta Anatomica Sinica. 2018, 49(2): 204-211 https://doi.org/10.16098/j.issn.0529-1356.2018.02.011

参考文献

[1]Meng L, Hu S, Huang L, et al.Papillary thyroid cancer coexisting with thyroid tuberculosis: a case report[J]. Oncol Lett, 2014, 7(5):1563-1565.
[2]Yoon SG, Yi JW, Seong CY, et al.Clinical characteristics of papillary thyroid carcinoma arising from the pyramidal lobe[J]. Ann Surg Treat Res, 2017, 92(3):123-128.
[3]Illam SP, Narayanankutty A, Mathew SE, et al. Epithelial mesenchymal transition in cancer progression: preventive Phytochemicals[J]. Recent Pat Anticancer Drug Discov, 2017, 12(3):234-246.
[4]May FE, Westley BR.TFF3 is a valuable predictive biomarker of endocrine response in metastatic breast cancer[J]. Endocr Relat Cancer, 2015, 22(3):465-479.
[5]Li Y, Sun Z, Liu K, et al.Prognostic significance of the co-expression of nucleophosmin and trefoil factor 3 in postoperative gastric cancer patients[J]. Mol Clin Oncol, 2014, 2(6):1055-1061.
[6]Xiao L, Liu YP, Xiao CX, et al.Serum TFF3 may be a pharamcodynamic marker of responses to chemotherapy in gastrointestinal cancers[J]. BMC Clin Pathol, 2014, 14(1):26.
[7]Zhang XJ,Wu JF,Huang J,et al. Expression and clinical significance of trefoil factor 3 in patiens with papillary thyroid carcinoma[J].Acta Anatomica Sinica, 2013(4):503-508. (in Chinese)
张小俊, 吴靖芳, 黄静, 等.三叶因子3在甲状腺乳头状癌中的表达及临床意义[J]. 解剖学报, 2013(4):503-508.
[8]Wu JF. Study on the effect and mechanism of RNA inference targeting TFF3 gene on the proliferation and invasion ability of papillary carcinoma cells[D]. Hebei Medical University, 2016. (in Chinese)
吴靖芳. RNA干扰TFF3基因对人甲状腺乳头状癌细胞增殖与侵袭的影响及机制研究[D].  河北医科大学, 2016. 
[9]You ML, Chen YJ, Chong QY, et al.Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular carcinoma is AKT-BCL-2 dependent[J]. Oncotarget, 2017, 8(24):39323-39344.
[10]Khoury T, Chadha K, Javle M, et al.Expression of intestinal trefoil factor (TFF-3) in hepatocellular carcinoma[J]. Int J Gastrointest Cancer, 2005, 35(3):171-177.
[11]Pandey V, Wu ZS, Zhang M, et al.Trefoil factor 3 promotes metastatic seeding and predicts poor survival outcome of patients with mammary carcinoma[J]. Breast Cancer Res, 2014, 16(5):429.
[12]Yuan Z, Chen D, Chen X, et al.Overexpression of trefoil factor 3 (TFF3) contributes to the malignant progression in cervical cancer cells[J]. Cancer Cell Int, 2017, 17(1):7.
[13]Hoffmann W.Trefoil factors TFF (trefoil factor family) peptide-triggered signals promoting mucosal restitution[J]. Cell Mol Life Sci, 2005, 62(24):2932-2938.
[14]Kannan N, Kang J, Kong X, et al.Trefoil factor 3 is oncogenic and mediates antiestrogen resistance in human mammary carcinoma[J]. Neoplasia, 2010, 12(12):1041-1053.
[15]Lamouille S, Xu J, Derynck R.Molecular mechanisms of epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Biol, 2014, 15(3):178-196.
[16]Romano S, Staibano S, Greco A, et al.FK506 binding protein 51 positively regulates melanoma stemness and metastatic potential[J]. Cell Death Dis, 2013, 4 (4):e578.
[17]Saxena M, Stephens MA, Pathak H, et al.Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters[J]. Cell Death Dis, 2011, 2 (7):e179.
[18]Zhao XL, Sun T, Che N, et al.Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator Twist1[J]. J Cell Mol Med, 2011, 15(3):691-700.
[19]Li S, Lu J, Chen Y, et al.MCP-1-induced ERK/GSK-3beta/Snail signaling facilitates the epithelial-mesenchymal transition and promotes the migration of MCF-7 human breast carcinoma cells[J]. Cell Mol Immunol, 2017, 14(7):621-630.
[20]Zhou Q, Chen J, Feng J, et al. SOSTDC1 inhibits follicular thyroid cancer cell proliferation, migration, and EMT via suppressing PI3K/Akt and MAPK/Erk signaling pathways[J]. Mol Cell Biochem, 2017, 435 (1-2):87-95.
[21] Baus-Loncar M, Giraud A. SMultiple regulatory pathways for trefoil factor (TFF) genes[J]. Cell Mol Life Sci, 2005, 62(24):2921-2931.
[22]Lin J, Sun Z, Zhang W, et al.Protective effects of intestinal trefoil factor (ITF) on gastric mucosal epithelium through activation of extracellular signal-regulated kinase 1/2 (ERK1/2)[J]. Mol Cell Biochem, 2015, 404(1-2):263-270.
[23]Xing M.Molecular pathogenesis and mechanisms of thyroid cancer[J]. Nat Rev Cancer, 2013, 13(3):184-199.

基金

三叶因子3在甲状腺乳头状癌中的作用机制及靶点筛选的联合研究;TFF3/RAS/RAF/MAPK在甲状腺乳头状癌细胞EMT中的作用

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