T Cell Factor 4, β-catenin and SFRP1 Expression of Wnt Signaling Pathway in Colorectal Carcinoma and the Prognosis_Journal of Biomedical Engineering

Authors：

 OUYurong ¹ , JINGGuiying ¹ , LIUJuan ¹ , GAOShan ² , CHENGZenong ¹ , DONGXiuqin ¹

1. Department of Pathology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233003, China;
2. Department of Pharmacology, Anhui Medical University, Hefei 230032, China;

Corresponding author：

OUYurong, Email: snowyc1220@163.com

Keywords：

colorectal carcinoma; T cell factor 4; β-catenin; secreted frizzled related protein 1; immunohistochemistry; prognosis

DOI：

10.7507/1001-5515.20150153

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Abnormal activation of Wnt signaling pathway is closely related to the occurrence of tumor, and T cell factor 4 (Tcf4) and β-catenin are important signal transmission factors of this pathway. The aim of the present study is to explore the significance and correlation between expression of Tcf4, β-catenin and secreted frizzled related protein 1(SFRP1), suppressor gene of Wnt signaling pathway, in colorectal carcinoma and their correlations to the clinicopathological factors. The expressions of Tcf4, β-catenin and SFRP1 were performed with immunohistochemistry staining in 97 cases of primary colorectal carcinoma and 40 cases of normal colorectal mucosa tissues. The results showed that the abnormal expression rates of Tcf4 and β-catenin in colorectal carcinoma were significantly higher than those in the control groups (P<0.01). The positive rate of SFRP1 was significantly lower than those in the control groups (P<0.01). The abnormal expression rates of Tcf4 and β-catenin were also related to the lymph node metastasis and Dukes stage (P<0.05). A significant correlation was found between the expressions of SFRP1 and Tcf4, β-catenin (P<0.05). Over-expression of Tcf4 and β-catenin was related to poor prognosis (P<0.05). But the survival rates of the group with SFRP1 expressions were higher than those in group without SFRP1 expressions (P<0.05). Cox multifactor regression analysis indicated that Dukes stage, expression of β-catenin and SFRP1 were independent risk factors of colorectal carcinoma (P<0.05). The results suggested that the abnormal expression of Tcf4 and β-catenin in colorectal cancer may be related to the reduced or absent expression of SFRP1. β-catenin accumulation in the nuclei formed complexes with Tcf4 is one of the important molecular switch maintaining colorectal malignant phenotype. The combined detection of these indexes may perform an important role in predicting the progression and prognosis of colorectal cancer, and could provide new molecular targets for gene treatment of colorectal cancer.

Citation： OUYurong, JINGGuiying, LIUJuan, GAOShan, CHENGZenong, DONGXiuqin. T Cell Factor 4, β-catenin and SFRP1 Expression of Wnt Signaling Pathway in Colorectal Carcinoma and the Prognosis. Journal of Biomedical Engineering, 2015, 32(4): 854-861. doi: 10.7507/1001-5515.20150153 Copy

1.	PANDURANGAN A K.Potential targets for prevention of colorectal cancer:a focus on PI3K/Akt/mTOR and Wnt pathways[J].Asian Pac J,2013,14(4):2201-2205.
2.	DONG L,ZHU J,WEN X,et al.Involvement of SET in the Wnt signaling pathway and the development of human colorectal cancer[J].Oncol Lett,2014,7(4):1203-1208.
3.	DOUCAS H,GARCEA G,NEAL C P,et al.Changes in the Wnt signalling pathway in gastrointestinal cancers and their prognostic significance[J].Eur J Cancer,2005,41(3):365-379.
4.	KORINEK V,BARKER N,MORIN P J,e t al.Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/-colon carcinoma[J].Science,1997,275(5307):1784-1787.
5.	FASOLINI M,WU X,FLOCCO M,e t al.Hot spots in Tcf4 for the interaction with beta-catenin[J].J Biol Chem,2003,278(23):21092-21098.
6.	ROOSE J,CLEVERS H.TCF transcription factors:molecular switches in carcinogenesis[J].Biochim Biophys Acta,1999,1424(2-3):M23-M27.
7.	MA B,ZHONG L,VAN BLITTERSWIJK C A,et al.T cell factor 4 is a pro-catabolic and apoptotic factor in human articular chondrocytes by potentiating nuclear factor κB signaling[J].J Biol Chem,2013,288(24):17552-17558.
8.	SUZUKI H,TOYOTA M,NOJIMA M,et al.SFRP,a family of new colorectal tumor suppressor candidate genes[J].Nippon Rinsho,2005,63(4):707-719.
9.	辛芝,孙蕾娜,潘毅.SFRP1基因表达与大肠肿瘤发生的关系研究[J].中国肿瘤临床,2008,35(6):323-326.
10.	ZHANG Y,CAO H Y,WANG E H.Frat1 and Tcf4 coexpression in non-small cell lung cancer (NSCLC)[J].Modern Oncology,2012,20(6):1175-1177.
11.	MARUYAMA K,OCHIAI A,AKIMOTO S,et al.Cytoplasmic beta-catenin accumulation as a predictor of hematogenous metastasis in human colorectal cancer[J].Oncology,2000,59(4):302-309.
12.	LEE C H,HUNG Y J,LIN C Y,et al.Loss of SFRP1 expression is associated with aberrant beta-catenin distribution and tumor progression in mucoepidermoid carcinoma of salivary glands.Ann Surg Oncol,2010,17(8):2237-2246.
13.	GORDON M D,NUSSE R.Wnt signaling:multiple pathways,multiple receptors,and multiple transcription factors[J].J Biol Chem,2006,281(32):22429-22433.
14.	AMIT S,HATZUBAI A,BIRMAN Y,et al.Axin-mediated CKI phosphorylation of beta-catenin at Ser 45:a molecular switch for the Wnt pathway[J].Genes,2002,16(9):1066-1076.
15.	KRIEGHOFF E,BEHRENS J,MAYR B.Nucleo-cytoplasmic distribution ofbeta-catenin is regulated by retention[J].J Cell Sci,2006,119(7):1453-1463.
16.	BUSH B M,BROCK A T,DENG J A,et al.The Wnt/β-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1 expression in colon cancer[J].Cell Biochem Funct,2013,31(3):228-236.
17.	POY F,LEPOURCELET M,SHIVDASANI R A,et al.Structure of a human Tcf4-beta-catenin complex[J].Nat Struct Biol,2001,8(12):1053-1057.
18.	HURLSTONE A,CLEVERS H.T-cell factors:turn-ons and turn-offs[J].EMBO J,2002,21(10):2303-2311.
19.	WANG J F,ZHOU Z G,WU D C H.Association of T cell factor-4 mRNA expression with clinicopathological characteristics of colorectal cancer[J].Chinese-German Journal of Clinical Oncology,2008,7(10):584-586.
20.	LYU Z,CHEN H,JIANG L,et al.Detection of RASSF2 and SFRP1 promoter region methylation in sporadic colorectal cancer patients[J].Zhonghua Wei Chang Wai Ke Za Zhi,2014,17(1):41-44.
21.	CHEN Y Z,LIU D,ZHAO Y X,et al.Aberrant promoter methylation of the SFRP1 gene may contribute to colorectal carcinogenesis:a meta-analysis[J].Tumour Biol,2014,35(9):9201-9210.

1. PANDURANGAN A K.Potential targets for prevention of colorectal cancer:a focus on PI3K/Akt/mTOR and Wnt pathways[J].Asian Pac J,2013,14(4):2201-2205.
2. DONG L,ZHU J,WEN X,et al.Involvement of SET in the Wnt signaling pathway and the development of human colorectal cancer[J].Oncol Lett,2014,7(4):1203-1208.
3. DOUCAS H,GARCEA G,NEAL C P,et al.Changes in the Wnt signalling pathway in gastrointestinal cancers and their prognostic significance[J].Eur J Cancer,2005,41(3):365-379.
4. KORINEK V,BARKER N,MORIN P J,e t al.Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/-colon carcinoma[J].Science,1997,275(5307):1784-1787.
5. FASOLINI M,WU X,FLOCCO M,e t al.Hot spots in Tcf4 for the interaction with beta-catenin[J].J Biol Chem,2003,278(23):21092-21098.
6. ROOSE J,CLEVERS H.TCF transcription factors:molecular switches in carcinogenesis[J].Biochim Biophys Acta,1999,1424(2-3):M23-M27.
7. MA B,ZHONG L,VAN BLITTERSWIJK C A,et al.T cell factor 4 is a pro-catabolic and apoptotic factor in human articular chondrocytes by potentiating nuclear factor κB signaling[J].J Biol Chem,2013,288(24):17552-17558.
8. SUZUKI H,TOYOTA M,NOJIMA M,et al.SFRP,a family of new colorectal tumor suppressor candidate genes[J].Nippon Rinsho,2005,63(4):707-719.
9. 辛芝,孙蕾娜,潘毅.SFRP1基因表达与大肠肿瘤发生的关系研究[J].中国肿瘤临床,2008,35(6):323-326.
10. ZHANG Y,CAO H Y,WANG E H.Frat1 and Tcf4 coexpression in non-small cell lung cancer (NSCLC)[J].Modern Oncology,2012,20(6):1175-1177.
11. MARUYAMA K,OCHIAI A,AKIMOTO S,et al.Cytoplasmic beta-catenin accumulation as a predictor of hematogenous metastasis in human colorectal cancer[J].Oncology,2000,59(4):302-309.
12. LEE C H,HUNG Y J,LIN C Y,et al.Loss of SFRP1 expression is associated with aberrant beta-catenin distribution and tumor progression in mucoepidermoid carcinoma of salivary glands.Ann Surg Oncol,2010,17(8):2237-2246.
13. GORDON M D,NUSSE R.Wnt signaling:multiple pathways,multiple receptors,and multiple transcription factors[J].J Biol Chem,2006,281(32):22429-22433.
14. AMIT S,HATZUBAI A,BIRMAN Y,et al.Axin-mediated CKI phosphorylation of beta-catenin at Ser 45:a molecular switch for the Wnt pathway[J].Genes,2002,16(9):1066-1076.
15. KRIEGHOFF E,BEHRENS J,MAYR B.Nucleo-cytoplasmic distribution ofbeta-catenin is regulated by retention[J].J Cell Sci,2006,119(7):1453-1463.
16. BUSH B M,BROCK A T,DENG J A,et al.The Wnt/β-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1 expression in colon cancer[J].Cell Biochem Funct,2013,31(3):228-236.
17. POY F,LEPOURCELET M,SHIVDASANI R A,et al.Structure of a human Tcf4-beta-catenin complex[J].Nat Struct Biol,2001,8(12):1053-1057.
18. HURLSTONE A,CLEVERS H.T-cell factors:turn-ons and turn-offs[J].EMBO J,2002,21(10):2303-2311.
19. WANG J F,ZHOU Z G,WU D C H.Association of T cell factor-4 mRNA expression with clinicopathological characteristics of colorectal cancer[J].Chinese-German Journal of Clinical Oncology,2008,7(10):584-586.
20. LYU Z,CHEN H,JIANG L,et al.Detection of RASSF2 and SFRP1 promoter region methylation in sporadic colorectal cancer patients[J].Zhonghua Wei Chang Wai Ke Za Zhi,2014,17(1):41-44.
21. CHEN Y Z,LIU D,ZHAO Y X,et al.Aberrant promoter methylation of the SFRP1 gene may contribute to colorectal carcinogenesis:a meta-analysis[J].Tumour Biol,2014,35(9):9201-9210.

Journal of Biomedical Engineering

T Cell Factor 4, β-catenin and SFRP1 Expression of Wnt Signaling Pathway in Colorectal Carcinoma and the Prognosis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content