开放期刊系统

DDR1低表达对结肠癌细胞增殖转移的影响

程 凰, 傅 晓娟, 何 建新

摘要

目的 探究DDR1( Discoidin domain receptor 1,DDR1)对结肠癌细胞增殖转移的影响及可能机制。方法 使用公共数据库GEPIA(Gene Expression Profiling Interactive Analysis)分析DDR1在人结肠癌组织和癌旁组织中的表达情况,蛋白质印迹实验(Western blot)检测DDR1在正常结肠上皮细胞FHC和结肠癌细胞(DLD-1、SW480、SW620和HCT-15)中蛋白表达量,使用平板克隆形成实验检测细胞增殖能力,Transwell小室迁移和侵袭实验检测细胞转移能力,蛋白质印迹实验检测MEK-ERK通路的变化。结果 DDR1在人结肠癌组织中表达水平高于癌旁组织(*P<0.05), shCon组(阴性对照组)的增殖转移能力明显强于shDDR1组(DDR1低表达组) (**P<0.01, ***P<0.001), Western blot结果显示, 与shCon组相比, shDDR1组p-MEK1/2(S217/221)和p-ERK1/2(T202/Y204)的蛋白表达水平下降。 结论 DDR1在人结肠癌组织和细胞中高表达,且DDR1促进人结肠癌细胞DLD-1和SW480增值转移,这可能是与MEK-ERK通路的磷酸化调控相关。

关键词

结肠癌;DDR1;迁移;侵袭

全文:

PDF

参考

[1]王玲玲,杨明,陈海鹏,等.早发性结直肠癌临床病理特征、诊治及筛查研究进展[J].肿瘤研究与临床,2021,33(11): 801-804.

[2]Adams R B, Haller D G, Roh M S. Improving resectability of hepatic colorectal metastases : expert consensus statement by Abdalla et al[J].Annals of Surgical Oncology,2006,13(10):1281-3.

[3]Ambrogio C,Gómez-López G Falcone M, et al. Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRA-driven lung adenocarcinoma [J]. Nat Med, 2016, 22(3): 270-7.

[4]Hu Y Liu J, Jiang B, et al. MiR-199a-5p loss up-regulated DDR1 aggravated colorectal cancer by activating epithelial-to-mesenchymal transition related signaling [J].Dig Dis Sci,2014, 59(9): 2163-72.

[5]Ram R, Lorente G,Nikolich K,et al. Discoidin domain receptor-la (DDR1a) promotes glioma cell invasion and adhesion in association with matrix metalloproteinase-2 [J].J Neurooncol,2006,76(3): 239.48.

[6]Park H S,Kim K R, Lee H J, et al. Overexpression of discoidin domain receptor 1 increases the migration and invasion of hepatocellular carcinoma cells in association with matrix metalloproteinase [J]. Oncol Rep,2007,18(6): 1435-41.

[7]Yang SH, Baek HA. Lee H J,et al. Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung carcinomas [J]. Oncol Rep,2010,24(2): 311-9.

[8]Richters A, Nguyen H D, Phan T, et al. Identification of type II and III DDR2 inhibitors [J].J Med Chem,2014, 57(10):4252-62.

[9]Neuhaus B,Bahren S, Bock B,et al. Migration inhibition of mammary epithelial cells by Syk is blocked in the presence of DDR1 receptors [J]. Cell Mol Life Sci,2011, 68(22): 3757-70.

[10]Saby C, Collin G, Sinane M, et al. DDRI and MT1-MMP Expression Levels Are Determinant for Triggering BIK-Mediated Apoptosis by 3D Type I Collagen Matrix in Invasive Basal-Like Breast Carcinoma Cells [J]. Front Pharmacol,2019,10:462.65

[11]Lu P, Weaver V M, Werb Z. The extracellular matrix: a dynamic niche in cancer progression [J]. J Cell Biol,2012, 196(4): 395-406.

[12]Yamanaka R, Arao T, Yajima N,et al. Identification of expressed genes characterizing long-term survival in malignant glioma patients [J]. Oncogene,2006,25(44): 5994-6002.

[13]Huang H, Svoboda R A, Lazenby A J, et al. Up-regulation of N-cadherin by Collagen I-activated Discoidin Domain Receptor 1in Pancreatic Cancer Requires the Adaptor Molecule Shel [J]. J Biol Chem,2016,291(44):23208-23.

[14]Cader FZ,Vockerodt M,Bose S, et al. The EBV oncogene LMP1 protects lymphoma cells from cell death through the collagen-mediated activation of DDR1 [J]. Blood,2013,122(26):4237-45.

[15]Vogel W, Abdulhussein R, Ford C. Sensing extracellular matrix: an update on discoidin domain receptor function [J]. Cellular signalling,2006,18(8): 1108-16

[16]Ikeda K, Wang L H, Torres R,et al. Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen [J]. J Biol Chem,2002, 277(21): 19206-12.

[17]Koo D H, McFadden C,Huang Y,et al. Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1 [J]. FEBS Lett, 2006, 580(1): 15-22.

[18]Das S, Ongusaha P P, Yang Y S, et al. Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance through nuclear factor-kappaBpathway activation [J]. Cancer Res,2006,66(16): 8123-30.

[19]Hansen C,Greengard P,Naim A C,et al.Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDRI [J].Exp Cell Res,2006,312(20): 4011-8.

[20]肖忠盛,龙泓,丁成明,等.IMP3基因沉默介导Notch信号通路对结直肠癌上皮间质转化及血管生成的影响[J].中国免疫学杂志,2020,36(14):1714⁃1719.

[21]Ongusaha P P, Kim JI, Fang L, et al. p53 induction and activation of DDR1 kinase counteract p53- mediated apoptosis and influence p53 regulation through a positive feedback loop [J]. Embo j,2003,22(6):1289-301.

[22]Sweeney S M, Orgel JP, Fertala A, et al. Candidate cell and matrix interaction domains on the collagen fibril, the predominant protein of vertebrates[J].JBiol Chem,2008,283(30):21187-97.

[23]Shintani Y, Fukumoto Y, ChaikaN, et al. Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1 [J].J Cell Biol, 2008,180(6): 1277-89.

[24]Yeh Y C, Wang C Z,Tang MJ.Discoidin domain receptor 1 activation suppresses alpha2betal integrin-dependent cell spreading through inhibition of Cdc42 activity[J].J Cell Physiol,2009,218(1):146-56.

[25]钟轩,王红钰,蒋涛,马等.干扰ZEB1表达对结直肠癌细胞上皮间质转化与增殖、凋亡与迁移的影响[J].实用医学 杂志,2019,35(21):3290⁃3295.


(0 摘要 Views, 0 PDF Downloads)

Refbacks

  • 当前没有refback。