您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2018, Vol. 56 ›› Issue (7): 57-64.doi: 10.6040/j.issn.1671-7554.0.2017.1216

• • 上一篇    

Yes相关蛋白与结肠癌病理因素的相关性

高振文,杨淑萍,谢雪雪,宋伟   

  1. 山东大学附属省立医院肿瘤微创综合治疗科, 山东 济南 250021
  • 发布日期:2022-09-27
  • 通讯作者: 宋伟. E-mail: sdslyysw@163.com
  • 基金资助:
    国家自然科学基金(81602332);山东省科技发展计划(2007GG30002024)

Correlation of Yes-associated protein and the pathological factors of colon cancer

GAO Zhenwen, YANG Shuping, XIE Xuexue, SONG Wei   

  1. Department of Minimally Invasive Tumor Therapies, Shandong Provincial Hospital Affiliated toShandong University, Jinan 250021, Shandong, China
  • Published:2022-09-27

摘要: 目的 探讨新型转录共激活因子Yes相关蛋白(YAP)的表达与结肠癌临床病理因素及肿瘤转移的相关性。 方法 选取104例组织蜡块,其中80例为结肠癌组织,24例为结肠癌转移灶组织。应用免疫组织化学法检测结肠癌原发灶及其多器官转移灶中YAP及N-钙黏蛋白的表达,应用qRT-PCR和Western blotting检测YAP、N-钙黏蛋白及E-钙黏蛋白在6种结肠癌细胞中的表达。 结果 N-钙黏蛋白在结肠癌原发灶组织中的阳性表达率高于结肠癌转移灶组织(P<0.05),而 YAP阳性表达率的差异无统计学意义(P>0.05)。YAP与N-钙黏蛋白的共同表达仅在结肠癌原发灶中呈正相关(r=0.5003,P<0.001),在结肠癌转移灶中两者的表达没有相关性(r=0.0325,P>0.05)。YAP及N-钙黏蛋白的阳性表达与肿瘤浸润深度及远处转移有关(P<0.05),而与肿瘤发生部位、大体形态、组织学类型、分化程度、肿瘤大小、淋巴结转移及脉管内癌栓无关(P>0.05)。在SW480、SW620、SW1116、DLD-1、HCT116和HT29这6种细胞中,YAP表达量的差异无统计学意义(P>0.05),E-钙黏蛋白在HT29和SW1116中的表达显著高于其他细胞,N-钙黏蛋白在HCT116和SW620中表达最高。 结论 YAP蛋白能够通过调控上皮-间质转化过程,促进结肠癌的发展及转移。

关键词: Yes相关蛋白, 结肠癌, 上皮-间质转化, N-钙黏蛋白, 原发灶, 转移灶

Abstract: Objective To investigate the expression of Yes-associated protein(YAP), a new transcriptional coactivator, and its correlation with the clincopathological factors and metastases of colon cancer. Methods A total of 104 paraffin embedded tissues were selected, including 80 colon cancer tissues and 24 metastatic tissues. The protein expressions of YAP and N-cadherin in the tissues were detected with immunohistochemical method. The expressions of YAP, E-cadherin and N-cadherin in six colon cancer cell lines were determined with qRT-PCR and Western blotting. Results There was no significant difference of YAP positive expression between the primary and metastatic colon cancer(P>0.05), while the positive expression of N-cadherin was significantly higher in primary colon cancer than in the metastatic cancer(P<0.05). There was positive correlation between YAP and N-cadherin in primary colon cancer(r=0.5003, P<0.001), but not in the metastatic cancer(r=0.0325, P>0.05). The positive expressions of YAP and N-cadherin were correlated with serosal invasion and distant metastases(P<0.05), not with anatomical and histological type, differentiation, tumor size, lymph node metastases, microvascular invasion, left-sided and right-sided colon cancer (P>0.05). In the six colorectal cancer cell lines(SW480, SW620, SW1116, DLD-1, HT29 and HCT116), there were no differences in the mRNA and protein expressions of YAP(P>0.05). E-cadherin was highly expressed in HT29 and 山 东 大 学 学 报 (医 学 版)56卷7期 -高振文,等.Yes相关蛋白与结肠癌病理因素的相关性 \=-SW1116, and N-cadherin was highly expressed in HCT116 and SW620. Conclusion YAP can promote the development and metastasis of colon cancer by regulating the epithelial-mesenchymal transition.

Key words: Yes-associated protein, Colon cancer, Epithelial-mesenchymal transition, N-cadherin, Primary tumor, Metastasis

中图分类号: 

  • R735.3
[1] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[2] Siegel R, Desantis C, Jemal A, et al. Colorectal cancer statistics, 2014[J]. CA Cancer J Clin, 2014, 64(2): 104-117.
[3] Pan D. Hippo signaling in organ size control[J]. Genes Dev, 2007, 21(8): 886-897.
[4] Pan D. The hippo signaling pathway in development and cancer[J]. Dev Cell, 2010, 19(4): 491-505.
[5] Maugeri-Saccà M, Barba M, Pizzuti L, et al. The Hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications[J]. Expert Rev Mol Med, 2015, 17: e14. doi: 10.1017/erm.2015.12.
[6] Wang S, Li H, Wang G, et al. Yes-associated protein(YAP)expression is involved in epithelial-mesenchymal transition in hepatocellular carcinoma[J]. Clin Transl Oncol, 2016, 18(2): 172-177.
[7] Zhou Z, Zhu JS, Gao CP, et al. siRNA targeting YAP gene inhibits gastric carcinoma growth and tumor metastasis in SCID mice[J]. Oncol Lett, 2016, 11(4): 2806-2814.
[8] Chaib I, Karachaliou N, Pilotto S, et al. Co-activation of STAT3 and YES-Associated Protein 1(YAP1)Pathway in EGFR-Mutant NSCLC[J]. J Natl Cancer Inst, 2017, 109(9). doi: 10.1093/jnci/djx014.
[9] Cho SY, Kim K, Park MS, et al. Expression of Yes-associated protein 1 and its clinical significance in ovarian serous cystadenocarcinoma[J]. Oncol Rep, 2017, 37(5): 2620-2632.
[10] Lamouille S, Xu J, Derynck R, et al. Molecular mechanisms of epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Biol, 2014, 15(3): 178-196.
[11] Harvey KF, Zhang X, Thomas DM, et al. The Hippo pathway and human cancer[J]. Nat Rev Cancer, 2013, 13(4): 246-257.
[12] Zanconato F, Cordenonsi M, Piccolo S, et al. YAP/TAZ at the roots of cancer[J]. Cancer Cell, 2016, 29(6): 783-803.
[13] Zhang H, Liu CY, Zha ZY, et al. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition[J]. J Biol Chem, 2009, 284(20): 13355-13362.
[14] Pefani DE, Pankova D, Abraham AG, et al. TGF-β targets the hippo pathway scaffold RASSF1A to facilitate YAP/SMAD2 nuclear translocation [J]. Mol Cell, 2016, 63(1): 156-166.
[15] Perumal N, Perumal M, Kannan A, et al. Morin impedes Yap nuclear translocation and fosters apoptosis through suppression of Wnt/β-catenin and NF-κB signaling in Mst1 overexpressed HepG2 cells [J]. Exp Cell Res, 2017, 355(2): 124-141.
[16] Zhang Y, Yuan J, Zhang X, et al. Angiomotin promotes the malignant potential of colon cancer cells by activating the YAP-ERK/PI3K-AKT signaling pathway [J]. Oncol Rep, 2016, 36(6): 3619-3626.
[17] Lee GH, Malietzis G, Askari A, et al. Is right-sided colon cancer different to left-sided colorectal cancer?-a systematic review[J]. Eur J Surg Oncol, 2015, 41(3): 300-308.
[18] Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions [J]. J Clin Invest, 2009, 119(6): 1429-1437.
[19] Iwatsuki M, Mimori K, Yokobori T, et al. Epithelial-mesenchymal transition in cancer development and its clinical significance[J]. Cancer Sci, 2010, 101(2): 293-299.
[20] Wang L, Shi S, Guo Z, et al. Overexpression of YAP and TAZ is an independent predictor of prognosis in colorectal cancer and related to the proliferation and metastasis of colon cancer cells[J]. PLoS One, 2013, 8(6): e65539. doi: 10.1371/journal.pone.0065539.
[21] Vassilev A, Kaneko KJ, Shu H, et al. TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm[J]. Genes Dev, 2001, 15(10): 1229-1241.
[22] Scoazec JY. Epithelial-mesenchymal transition and colon cancer[J]. Ann Pathol, 2009, 29 Spec No 1:S63-64. doi: 10.1016/j.annpat.2009.07.037.
[23] Nawa T, Kato J, Kawamoto H, et al. Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology[J]. J Gastroenterol Hepatol, 2008, 23(3): 418-423.
[24] 刘传玲, 张晓东. 左右半结肠癌的差异及临床治疗理念[J]. 中国肿瘤临床, 2016, 43(18): 787-791. LIU Chuanling, ZHANG Xiaodong. Comparison and treatment of left- and right-side colon cancer [J]. Chinese Journal of Clinical Oncology, 2016, 43(18): 787-791.
[25] Shao DD, Xue W, Krall EB, et al. KRAS and YAP1 converge to regulate EMT and tumor survival [J]. Cell, 2014, 158(1): 171-184.
[1] 林雪艳,张灿灿,田民乐,田永杰. 聚腺苷酸二磷酸核糖聚合酶-1在子宫内膜异位症中的表达及意义[J]. 山东大学学报 (医学版), 2022, 60(2): 27-31.
[2] 薛源,林雪艳,徐歌,田永杰. 低氧诱导因子-1α在子宫内膜异位症患者血清中的表达和对在位子宫内膜间质细胞上皮-间质转化的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 41-47.
[3] 甄秋来,吕欣然,叶辉,丁绪超,柴小雪,胡辛,周明,曹莉莉. 基于TCGA数据库预测结肠癌预后基因及其临床应用价值[J]. 山东大学学报 (医学版), 2021, 59(1): 64-71.
[4] 王宝金,赵欣欣,李霞,马倩,王新月,孙阳,史中娜. miR-203靶向Survivin抑制卵巢癌细胞增殖、迁移与侵袭[J]. 山东大学学报 (医学版), 2020, 58(12): 23-28.
[5] 洪甲庚,聂洋洋,苏国强. 丙泊酚对结肠癌细胞增殖、迁移及Wnt1和β-catenin表达的影响[J]. 山东大学学报 (医学版), 2020, 58(11): 53-58.
[6] 林雪艳,李春艳,侯小满,田永杰. PARP-1及EMT标志物在子宫腺肌病在位及异位内膜中的表达[J]. 山东大学学报(医学版), 2017, 55(9): 36-40.
[7] 王贲士, 单军奇,侯庆生,公为鹏,朱振宇,郭洪亮. CD11b+/CD66b-表型髓系细胞在结肠癌进展和肝转移中的作用[J]. 山东大学学报(医学版), 2017, 55(10): 41-45.
[8] 刘惠苓,王兴文,冯少滨,冯虹,韩俊庆. B类I型清道夫受体的高表达与结肠癌患者预后的相关性[J]. 山东大学学报(医学版), 2017, 55(10): 84-89.
[9] 张雪群,高卫,潘盼,高骏逸. PI3K/AKT及其相关因子在结肠癌中的表达[J]. 山东大学学报(医学版), 2016, 54(1): 52-57.
[10] 张晓晖, 颜磊, 齐莎莎, 路真真, 李明江, 赵兴波. 子宫内膜腺癌中EMT的发生及miR200a/ZEB1信号通路在该过程中发挥的作用[J]. 山东大学学报(医学版), 2015, 53(7): 48-52.
[11] 王尧, 陈艳红, 陈宏. 结肠癌患者外周血DPYD基因多态性与5-FU敏感性和毒副作用相关性分析[J]. 山东大学学报(医学版), 2014, 52(S1): 18-21.
[12] 孟宪鹏1,刘杰2,苏娅3,邴雪4,高卫2. SU11274对人结肠癌LOVO细胞裸鼠移植瘤的抑制作用[J]. 山东大学学报(医学版), 2014, 52(2): 20-24.
[13] 李雪梅1, 颜世平1, 宿敬然2,程兆令1, 朱强1. TIPE2在结肠癌发展中的作用及分子机制[J]. 山东大学学报(医学版), 2014, 52(1): 20-22.
[14] 孙秀梅1,高峰2,刘子凤3. 盐霉素对结肠癌干细胞特性的抑制作用[J]. 山东大学学报(医学版), 2013, 51(9): 40-44.
[15] 任鹏1,郝青2,王杰书3,李洪林3,李波3,王峰3. 趋化因子受体3及血管生成拟态在结肠癌肝转移中的作用[J]. 山东大学学报(医学版), 2012, 50(8): 96-99.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!