Skip to main content
Top
Published in: International Journal of Colorectal Disease 3/2006

01-04-2006 | Original Article

An increase in the number of adhesion proteins with altered expression is associated with an increased risk of cancer death for colon carcinoma patients

Authors: Johan Bondi, Geir Bukholm, Jahn M. Nesland, Arne Bakka, Ida R. K. Bukholm

Published in: International Journal of Colorectal Disease | Issue 3/2006

Login to get access

Abstract

Background and aims

Reduced expression of components of the cell–cell adhesive cadherin–catenin complex has been related to the invasive phenotype in many malignancies, but the prognostic value of altered expression of its separate components varies in colon cancer. Our objective was evaluation of the cadherin–catenin complex, considered as a functional unit, in colon carcinomas and its relationship to patient outcome.

Patients and methods

Tumours from 206 patients operated for colon adenocarcinoma were analysed using immunohistochemistry of E-cadherin, α, β, and γ-catenins, and p120ctn. The sum of proteins with altered membranous expression was calculated as an overall adhesion score (ranging from 0 to 5) for each patient. The results were correlated with patient outcome.

Results

Of the tumours included in the analysis 0.5% had score 0, 4.9% had score 1, 13.6% had score 2, 31.6% had score 3, 33.0% had score 4, and 16.5% tumours had score 5. None of the proteins examined had individual, independent prognostic value. However, an increase in the number of proteins in the cadherin–catenin complex with altered expression was associated with an increased risk of cancer death (univariate P=0.002; multivariate P=0.007, HR 1.48, 95% CI 1.11–1.96).

Conclusions

An increase in the number of adhesion proteins with altered expression in the primary tumour is associated with increasingly impaired prognosis for patients operated for colon carcinoma. The results reveal that the entire cadherin–catenin complex should be evaluated when assessing its prognostic value in the disease.
Literature
1.
go back to reference Wijnhoven BPL, Dinjens WNM, Pignatelli M (2000) E-cadherin–catenin cell–cell adhesion complex and human cancer. Br J Surg 87:992–1005CrossRefPubMed Wijnhoven BPL, Dinjens WNM, Pignatelli M (2000) E-cadherin–catenin cell–cell adhesion complex and human cancer. Br J Surg 87:992–1005CrossRefPubMed
2.
go back to reference Boller K, Vestweber D, Kemler R (1985) Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells. J Cell Biol 100:327–332 Boller K, Vestweber D, Kemler R (1985) Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells. J Cell Biol 100:327–332
3.
go back to reference Herrenknecht K, Ozawa M, Eckerskorn C, Lottspeich F, Lenter M, Kemler R (1991) The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. Proc Natl Acad Sci U S A 88:9156–9160PubMed Herrenknecht K, Ozawa M, Eckerskorn C, Lottspeich F, Lenter M, Kemler R (1991) The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. Proc Natl Acad Sci U S A 88:9156–9160PubMed
4.
go back to reference McCrea PD, Turck CW, Gumbiner B (1991) A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science 254:1359–1361PubMed McCrea PD, Turck CW, Gumbiner B (1991) A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science 254:1359–1361PubMed
5.
go back to reference Nagafuchi A, Takeichi M, Tsukita S (1991) The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell 65:849–857CrossRefPubMed Nagafuchi A, Takeichi M, Tsukita S (1991) The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell 65:849–857CrossRefPubMed
6.
go back to reference Ben Ze’ev A, Geiger B (1998) Differential molecular interactions of beta-catenin and plakoglobin in adhesion, signaling and cancer. Curr Opin Cell Biol 10:629–639CrossRefPubMed Ben Ze’ev A, Geiger B (1998) Differential molecular interactions of beta-catenin and plakoglobin in adhesion, signaling and cancer. Curr Opin Cell Biol 10:629–639CrossRefPubMed
7.
go back to reference Oyama T, Kanai Y, Ochiai A, Akimoto S, Oda T, Yanagihara K et al (1994) A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res 54:6282–6287 Oyama T, Kanai Y, Ochiai A, Akimoto S, Oda T, Yanagihara K et al (1994) A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res 54:6282–6287
8.
go back to reference Daniel JM, Reynolds AB (1995) The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. Mol Cell Biol 15:4819–4824PubMed Daniel JM, Reynolds AB (1995) The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. Mol Cell Biol 15:4819–4824PubMed
9.
go back to reference Daniel JM, Reynolds AB (1997) Tyrosine phosphorylation and cadherin/catenin function. BioEssays 19:883–891CrossRefPubMed Daniel JM, Reynolds AB (1997) Tyrosine phosphorylation and cadherin/catenin function. BioEssays 19:883–891CrossRefPubMed
10.
go back to reference Bringuier PP, Umbas R, Schaafsma HE, Karthaus HF, Debruyne FM, Schalken JA (1993) Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res 53:3241–3245 Bringuier PP, Umbas R, Schaafsma HE, Karthaus HF, Debruyne FM, Schalken JA (1993) Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res 53:3241–3245
11.
go back to reference Bukholm IK, Nesland JM, Karesen R, Jacobsen U, Borresen-Dale AL (1998) E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol 185:262–266CrossRefPubMed Bukholm IK, Nesland JM, Karesen R, Jacobsen U, Borresen-Dale AL (1998) E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol 185:262–266CrossRefPubMed
12.
go back to reference Gamallo C, Palacios J, Suarez A, Pizarro A, Navarro P, Quintanilla M et al (1993) Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol 142:987–993PubMed Gamallo C, Palacios J, Suarez A, Pizarro A, Navarro P, Quintanilla M et al (1993) Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol 142:987–993PubMed
13.
go back to reference Ikeguchi M, Taniguchi T, Makino M, Kaibara N (2000) Reduced E-cadherin expression and enlargement of cancer nuclei strongly correlate with hematogenic metastasis in colorectal adenocarcinoma. Scand J Gastroenterol 35:839–846CrossRefPubMed Ikeguchi M, Taniguchi T, Makino M, Kaibara N (2000) Reduced E-cadherin expression and enlargement of cancer nuclei strongly correlate with hematogenic metastasis in colorectal adenocarcinoma. Scand J Gastroenterol 35:839–846CrossRefPubMed
14.
go back to reference Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW et al (1993) E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res 53:1690–1695 Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW et al (1993) E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res 53:1690–1695
15.
go back to reference Schipper JH, Frixen UH, Behrens J, Unger A, Jahnke K, Birchmeier W (1991) E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res 51:6328–6337 Schipper JH, Frixen UH, Behrens J, Unger A, Jahnke K, Birchmeier W (1991) E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res 51:6328–6337
16.
go back to reference Raftopoulos I, Davaris P, Karatzas G, Karayannacos P, Kouraklis G (1998) Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival. J Surg Oncol 68:92–99CrossRefPubMed Raftopoulos I, Davaris P, Karatzas G, Karayannacos P, Kouraklis G (1998) Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival. J Surg Oncol 68:92–99CrossRefPubMed
17.
go back to reference Brabletz T, Jung A, Dag S, Hlubek F, Kirchner T (1999) Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol 155:1033–1038PubMed Brabletz T, Jung A, Dag S, Hlubek F, Kirchner T (1999) Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol 155:1033–1038PubMed
18.
go back to reference He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT et al (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512CrossRefPubMed He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT et al (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512CrossRefPubMed
19.
go back to reference Kolligs FT, Kolligs B, Hajra KM, Hu G, Tani M, Cho KR et al (2000) Gamma-catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta-catenin. Genes Dev 14:1319–1331PubMed Kolligs FT, Kolligs B, Hajra KM, Hu G, Tani M, Cho KR et al (2000) Gamma-catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta-catenin. Genes Dev 14:1319–1331PubMed
20.
go back to reference Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426CrossRefPubMed Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426CrossRefPubMed
21.
go back to reference Daniel JM, Reynolds AB (1999) The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol Cell Biol 19:3614–3623PubMed Daniel JM, Reynolds AB (1999) The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol Cell Biol 19:3614–3623PubMed
22.
go back to reference Kinch MS, Clark GJ, Der CJ, Burridge K (1995) Tyrosine phosphorylation regulates the adhesions of RAS-transformed breast epithelia. J Cell Biol 130:461–471CrossRefPubMed Kinch MS, Clark GJ, Der CJ, Burridge K (1995) Tyrosine phosphorylation regulates the adhesions of RAS-transformed breast epithelia. J Cell Biol 130:461–471CrossRefPubMed
23.
go back to reference Sommers CL, Gelmann EP, Kemler R, Cowin P, Byers SW (1994) Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells. Cancer Res 54:3544–3552 Sommers CL, Gelmann EP, Kemler R, Cowin P, Byers SW (1994) Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells. Cancer Res 54:3544–3552
24.
go back to reference van der Wurff AA, Vermeulen SJ, van der Linden EP, Mareel MM, Bosman FT, Arends JW (1997) Patterns of alpha- and beta-catenin and E-cadherin expression in colorectal adenomas and carcinomas. J Pathol 182:325–330CrossRefPubMed van der Wurff AA, Vermeulen SJ, van der Linden EP, Mareel MM, Bosman FT, Arends JW (1997) Patterns of alpha- and beta-catenin and E-cadherin expression in colorectal adenomas and carcinomas. J Pathol 182:325–330CrossRefPubMed
25.
go back to reference Dukes CE (1932) The classification of cancer in the rectum. J Pathol Bacteriol 35:323 Dukes CE (1932) The classification of cancer in the rectum. J Pathol Bacteriol 35:323
26.
go back to reference Morton RA, Ewing CM, Nagafuchi A, Tsukita S, Isaacs WB (1993) Reduction of E-cadherin levels and deletion of the alpha-catenin gene in human prostate cancer cells. Cancer Res 53:3585–3590 Morton RA, Ewing CM, Nagafuchi A, Tsukita S, Isaacs WB (1993) Reduction of E-cadherin levels and deletion of the alpha-catenin gene in human prostate cancer cells. Cancer Res 53:3585–3590
27.
go back to reference Shimoyama Y, Nagafuchi A, Fujita S, Gotoh M, Takeichi M, Tsukita S et al (1992) Cadherin dysfunction in a human cancer cell line: possible involvement of loss of alpha-catenin expression in reduced cell–cell adhesiveness. Cancer Res 52:5770–5774 Shimoyama Y, Nagafuchi A, Fujita S, Gotoh M, Takeichi M, Tsukita S et al (1992) Cadherin dysfunction in a human cancer cell line: possible involvement of loss of alpha-catenin expression in reduced cell–cell adhesiveness. Cancer Res 52:5770–5774
28.
go back to reference Ghadimi BM, Behrens J, Hoffmann I, Haensch W, Birchmeier W, Schlag PM (1999) Immunohistological analysis of E-cadherin, alpha-, beta- and gamma-catenin expression in colorectal cancer: implications for cell adhesion and signaling. Eur J Cancer 35:60–65 Ghadimi BM, Behrens J, Hoffmann I, Haensch W, Birchmeier W, Schlag PM (1999) Immunohistological analysis of E-cadherin, alpha-, beta- and gamma-catenin expression in colorectal cancer: implications for cell adhesion and signaling. Eur J Cancer 35:60–65
29.
go back to reference Gold JS, Reynolds AB, Rimm DL (1998) Loss of p120ctn in human colorectal cancer predicts metastasis and poor survival. Cancer Lett 132:193–201CrossRefPubMed Gold JS, Reynolds AB, Rimm DL (1998) Loss of p120ctn in human colorectal cancer predicts metastasis and poor survival. Cancer Lett 132:193–201CrossRefPubMed
30.
go back to reference Hugh TJ, Dillon SA, Taylor BA, Pignatelli M, Poston GJ, Kinsella AR (1999) Cadherin–catenin expression in primary colorectal cancer: a survival analysis. Br J Cancer 80:1046–1051CrossRefPubMed Hugh TJ, Dillon SA, Taylor BA, Pignatelli M, Poston GJ, Kinsella AR (1999) Cadherin–catenin expression in primary colorectal cancer: a survival analysis. Br J Cancer 80:1046–1051CrossRefPubMed
31.
go back to reference Jiang WG (1996) E-cadherin and its associated protein catenins, cancer invasion and metastasis. Br J Surg 83:437–446PubMed Jiang WG (1996) E-cadherin and its associated protein catenins, cancer invasion and metastasis. Br J Surg 83:437–446PubMed
32.
go back to reference Bondi J, Bukholm G, Nesland JM, Bukholm IR (2004) Expression of non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 in relation to patient outcome in human colon adenocarcinomas. APMIS 112:49–56CrossRefPubMed Bondi J, Bukholm G, Nesland JM, Bukholm IR (2004) Expression of non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 in relation to patient outcome in human colon adenocarcinomas. APMIS 112:49–56CrossRefPubMed
33.
go back to reference Chen X, Kojima S, Borisy GG, Green KJ (2003) p120 catenin associates with kinesin and facilitates the transport of cadherin–catenin complexes to intercellular junctions. J Cell Biol 163:547–557CrossRefPubMed Chen X, Kojima S, Borisy GG, Green KJ (2003) p120 catenin associates with kinesin and facilitates the transport of cadherin–catenin complexes to intercellular junctions. J Cell Biol 163:547–557CrossRefPubMed
34.
go back to reference Davis MA, Ireton RC, Reynolds AB (2003) A core function for p120-catenin in cadherin turnover. J Cell Biol 163:525–534CrossRefPubMed Davis MA, Ireton RC, Reynolds AB (2003) A core function for p120-catenin in cadherin turnover. J Cell Biol 163:525–534CrossRefPubMed
35.
go back to reference Thoreson MA, Reynolds AB (2002) Altered expression of the catenin p120 in human cancer: implications for tumor progression. Differentiation 70:583–589CrossRefPubMed Thoreson MA, Reynolds AB (2002) Altered expression of the catenin p120 in human cancer: implications for tumor progression. Differentiation 70:583–589CrossRefPubMed
36.
go back to reference Anastasiadis PZ, Reynolds AB (2000) The p120 catenin family: complex roles in adhesion, signaling and cancer. J Cell Sci 113(Pt 8):1319–1334PubMed Anastasiadis PZ, Reynolds AB (2000) The p120 catenin family: complex roles in adhesion, signaling and cancer. J Cell Sci 113(Pt 8):1319–1334PubMed
Metadata
Title
An increase in the number of adhesion proteins with altered expression is associated with an increased risk of cancer death for colon carcinoma patients
Authors
Johan Bondi
Geir Bukholm
Jahn M. Nesland
Arne Bakka
Ida R. K. Bukholm
Publication date
01-04-2006
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 3/2006
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-005-0762-1

Other articles of this Issue 3/2006

International Journal of Colorectal Disease 3/2006 Go to the issue