SOX2/CDX2/HNF4α在食管癌中的研究进展
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摘要
性别决定区Y框蛋白2(SRY related HMG box-2,SOX2)基因是基本的干细胞基因之一,其编码的SOX2蛋白也是维持胚胎干细胞及多种组织干细胞自我更新及增殖能力的重要转录因子。尾侧型同源转录因子2(caudal type homeobox transcription factor-2,CDX2)是一种肠特异性转录因子,在调节肠道基因表达与肠道发育及对肠道上皮细胞分化、增殖方面具有重要作用。近年来有研究结果显示,SOX2、CDX2在barrett食管及部分食管癌中存在异常表达,参与食管癌细胞的不同生物学行为。肝细胞核因子(hepatocyte nuclear factor,HNF)4α属于细胞核受体超家族成员,有文献报道,HNF4α过表达在成人食管上皮细胞模型中诱导肠柱状上皮表达,提示HNF4α是一种可能在食管上皮细胞中产生柱状化生的关键基因。因此,本文就SOX2、CDX2及HNF4α与食管癌的研究进展给予综述。
The SOX2 gene is one of the basic stem cell genes, and its encoded SOX2 protein is also an important transcription factor for maintaining the self-renewal and proliferation of embryonic stem cells and various tissue stem cells. CDX 2 is an intestinal specific transcription factor that plays an important role in regulating intestinal gene expression and intestinal development and differentiation and proliferation of intestinal epithelial cells. In recent years, studies have shown that SOX2 and CDX2 are abnormally expressed in barrett's esophagus and partial esophageal cancer, and participate in different biological behaviors of esophageal cancer cells. HNF4α belongs to the nuclear receptor superfamily. It has been reported in the literature that HNF4α overexpression induces intestinal columnar epithelial expression in the adult esophageal epithelial cell model, suggesting that HNF4α is a key gene that may produce columnar metaplasia in esophageal epithelial cells. Therefore, this article reviews the research progress of SOX2, CDX2 and HNF4α and esophageal cancer.
The SOX2 gene is one of the basic stem cell genes, and its encoded SOX2 protein is also an important transcription factor for maintaining the self-renewal and proliferation of embryonic stem cells and various tissue stem cells. CDX 2 is an intestinal specific transcription factor that plays an important role in regulating intestinal gene expression and intestinal development and differentiation and proliferation of intestinal epithelial cells. In recent years, studies have shown that SOX2 and CDX2 are abnormally expressed in barrett's esophagus and partial esophageal cancer, and participate in different biological behaviors of esophageal cancer cells. HNF4α belongs to the nuclear receptor superfamily. It has been reported in the literature that HNF4α overexpression induces intestinal columnar epithelial expression in the adult esophageal epithelial cell model, suggesting that HNF4α is a key gene that may produce columnar metaplasia in esophageal epithelial cells. Therefore, this article reviews the research progress of SOX2, CDX2 and HNF4α and esophageal cancer.
引文
[1]Chen W,Sun K,Zheng R,et al.Cancer incidence and mortality in China,2014[J].Chin J Cancer Res,2018,30(1):1-12.
[2]杨建杰,张玉林.COX2、CDX2在糜烂性食管炎、Barrate食管及食管腺癌中的表达及意义[J].检验医学与临床,2017,14(11):1621-1623.
[3]Kelberman D,Rizzoti K,Avilion A,et al.Mutations within Sox2/SOX2 are associated with abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans[J].J Clin Invest,2006,116(9):2442-2455.
[4]Gen Y,Yasui K,Zen Y,et al.SOX2 identified as a target gene for the amplification at 3q26 that is frequently detected in esophageal squamous cell carcinoma[J].Cancer Genet Cytogenet,2010,202(2):82-93.
[5]Boumahdi S,Driessens G,Lapouge G,et al.SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma[J].Nature,2014,511(7508):246-250.
[6]Gao H,Teng C,Huang W,et al.SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-alpha Signaling[J].Int JMol Sci,2015,16(9):21643-21657.
[7]Gen Y,Yasui K,Nishikawa T,et al.SOX2 promotes tumor growth of esophageal squamous cell carcinoma through the AKT/mammalian target of rapamycin complex 1 signaling pathway[J].Cancer Sci,2013,104(7):810-816.
[8]Forghanifard M.M,Ardalan Khales S,Javdani-Mallak A,et al.Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma[J].Med Oncol,2014,31(4):922.
[9]陈清江,张明治.SOX2在食管鳞癌组织中的表达及意义[J].世界华人消化杂志,2011,19(16):1698-1703.
[10]陈伟妍,李桂艳,辛春,等.食管癌组织中MTA1、SOX2的表达及与预后的关系研究[J].中国现代手术学杂志,2017,21(4):251-256.
[11]Maehara R,Fujikura K,Takeuchi K,et al.SOX2-silenced squamous cell carcinoma:a highly malignant form of esophageal cancer with SOX2promoter hypermethylation[J].Mod Pathol,2018,31(1):83-92.
[12]张晖,周顺军,胡文聪.干细胞转录因子OCT4、SOX2在食管鳞癌中的表达及与预后的关系[J].中国现代医学杂志,2017,27(13):58-62.
[13]张利云.转录因子SOX2、Oct4在食管癌中的表达及其相互关系[J].延安大学,2012:39.
[14]Chuang WY,Chang YS,Chao YK,et al.High sex determining region Y-box 2(SOX2)expression correlates with absence of nodal metastasis in esophageal squamous cell carcinoma[J].Int J Clin Exp Pathol,2015,8(8):9248-9255.
[15]解智慧.干细胞转录调控因子SOX2在食管鳞癌中的表达与临床预后的关系[J].郑州大学,2013:65.
[16]Ten KF,van Olphen SH,Bruno MJ,et al.Loss of SRY-box2(SOX2)expression and its impact on survival of patients with oesophageal adenocarcinoma[J].Br J Surg,2017,104(10):1327-1337.
[17]Lynch JP,Silberg DG.To differentiate or proliferate?The interaction between PI3K/PTEN and Cdx2[J].Gastroenterology,2002,123(4):1395-1397.
[18]马丽萍,李娜,潘秀英,等.同源异型盒基因CDX1和CDX2使食管腺癌细胞恶性降低[J].基础医学与临床,2006,26(12):1319-1323.
[19]王再兴,薛麟,王岩,等.CDX2、Hep在Barrett食管中的表达及其临床意义[J].宁夏医学杂志,2013,35(1):29-31.
[20]许良璧,项一宁,杨浩羿,等.糜烂性食管炎、Barrett食管及食管腺癌中SOX2、CDX2的表达及其临床意义[J].临床与实验病理学杂志,2016,32(9):1014-1018.
[21]Odom DT,Zizlsperger N,Gordon DB,et al.Control of pancreas and liver gene expression by HNF transcription factors[J].Science,2004,303(5662):1378-1381.
[22]Tanaka T,Jiang S,Hotta H,et al.Dysregulated expression of P1 and P2promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer[J].J Pathol,2006,208(5):662-672.
[23]Colleypriest BJ,Burke ZD,Griffiths LP,et al.Hnf4alpha is a key gene that can generate columnar metaplasia in oesophageal epithelium[J].Differentiation,2017,93:39-49.
[24]Green NH,Nicholls Z,Heath PR,et al.Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa[J].Int J Exp Pathol,2014,95(3):216-228.
[2]杨建杰,张玉林.COX2、CDX2在糜烂性食管炎、Barrate食管及食管腺癌中的表达及意义[J].检验医学与临床,2017,14(11):1621-1623.
[3]Kelberman D,Rizzoti K,Avilion A,et al.Mutations within Sox2/SOX2 are associated with abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans[J].J Clin Invest,2006,116(9):2442-2455.
[4]Gen Y,Yasui K,Zen Y,et al.SOX2 identified as a target gene for the amplification at 3q26 that is frequently detected in esophageal squamous cell carcinoma[J].Cancer Genet Cytogenet,2010,202(2):82-93.
[5]Boumahdi S,Driessens G,Lapouge G,et al.SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma[J].Nature,2014,511(7508):246-250.
[6]Gao H,Teng C,Huang W,et al.SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-alpha Signaling[J].Int JMol Sci,2015,16(9):21643-21657.
[7]Gen Y,Yasui K,Nishikawa T,et al.SOX2 promotes tumor growth of esophageal squamous cell carcinoma through the AKT/mammalian target of rapamycin complex 1 signaling pathway[J].Cancer Sci,2013,104(7):810-816.
[8]Forghanifard M.M,Ardalan Khales S,Javdani-Mallak A,et al.Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma[J].Med Oncol,2014,31(4):922.
[9]陈清江,张明治.SOX2在食管鳞癌组织中的表达及意义[J].世界华人消化杂志,2011,19(16):1698-1703.
[10]陈伟妍,李桂艳,辛春,等.食管癌组织中MTA1、SOX2的表达及与预后的关系研究[J].中国现代手术学杂志,2017,21(4):251-256.
[11]Maehara R,Fujikura K,Takeuchi K,et al.SOX2-silenced squamous cell carcinoma:a highly malignant form of esophageal cancer with SOX2promoter hypermethylation[J].Mod Pathol,2018,31(1):83-92.
[12]张晖,周顺军,胡文聪.干细胞转录因子OCT4、SOX2在食管鳞癌中的表达及与预后的关系[J].中国现代医学杂志,2017,27(13):58-62.
[13]张利云.转录因子SOX2、Oct4在食管癌中的表达及其相互关系[J].延安大学,2012:39.
[14]Chuang WY,Chang YS,Chao YK,et al.High sex determining region Y-box 2(SOX2)expression correlates with absence of nodal metastasis in esophageal squamous cell carcinoma[J].Int J Clin Exp Pathol,2015,8(8):9248-9255.
[15]解智慧.干细胞转录调控因子SOX2在食管鳞癌中的表达与临床预后的关系[J].郑州大学,2013:65.
[16]Ten KF,van Olphen SH,Bruno MJ,et al.Loss of SRY-box2(SOX2)expression and its impact on survival of patients with oesophageal adenocarcinoma[J].Br J Surg,2017,104(10):1327-1337.
[17]Lynch JP,Silberg DG.To differentiate or proliferate?The interaction between PI3K/PTEN and Cdx2[J].Gastroenterology,2002,123(4):1395-1397.
[18]马丽萍,李娜,潘秀英,等.同源异型盒基因CDX1和CDX2使食管腺癌细胞恶性降低[J].基础医学与临床,2006,26(12):1319-1323.
[19]王再兴,薛麟,王岩,等.CDX2、Hep在Barrett食管中的表达及其临床意义[J].宁夏医学杂志,2013,35(1):29-31.
[20]许良璧,项一宁,杨浩羿,等.糜烂性食管炎、Barrett食管及食管腺癌中SOX2、CDX2的表达及其临床意义[J].临床与实验病理学杂志,2016,32(9):1014-1018.
[21]Odom DT,Zizlsperger N,Gordon DB,et al.Control of pancreas and liver gene expression by HNF transcription factors[J].Science,2004,303(5662):1378-1381.
[22]Tanaka T,Jiang S,Hotta H,et al.Dysregulated expression of P1 and P2promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer[J].J Pathol,2006,208(5):662-672.
[23]Colleypriest BJ,Burke ZD,Griffiths LP,et al.Hnf4alpha is a key gene that can generate columnar metaplasia in oesophageal epithelium[J].Differentiation,2017,93:39-49.
[24]Green NH,Nicholls Z,Heath PR,et al.Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa[J].Int J Exp Pathol,2014,95(3):216-228.