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Dominant expression of 85-kDa form of cortactin in colorectal cancer

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Abstract

Purpose: Cortactin is commonly expressed in several human cancers, which may alter their invasive or metastatic properties. Eighty five kilodalton form (p85) and 80-kDa form (p80) of cortactin are two separate bands in SDS-PAGE representing different conformational states. The objective of this study was to investigate cortactin expression in colorectal cancer (CRC). Experimental Design: Cortactin expression was studied in an eight paired laser capture microdissection (LCM) CRC tissues and matched non-cancerous epithelia by immunoblotting. The expression in 58 CRC and two cell lines, HCT8 and HCT116, was studied respectively by immunohistochemistry and confocal laser scanning immunofluorescence. Results: Dominant expression of p85 was identified in LCM-procured CRC tissues compared with equal intensity of p85 and p80 forms in non-cancerous tissues, while the amount of total cortactin was approximate. Immunohistochemistry analysis demonstrated that cortactin located in the cytoplasm of tumor cells and adjacent non-cancerous cells, and its expression was negatively correlated with TNM staging and lymphatic invasion status. However, the invasion fronts in 3 of 58 primary tumors and 28 of 39 available lymph node metastases were intensively stained. Further, immunofluorescence analysis showed that cortactin was distributed in cytoplasm and enriched in the front of the extending lamellipodia at adhering side of cultured cancer cells. Conclusions: Our results demonstrated the dominant expression of p85 form of cortactin in CRC for the first time. The enrichment of cortactin in the invasion front of some tumor cells and in the extending lamellipodia of cultured cancer cells suggests that cortactin may help cancer cell movement.

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Abbreviations

CRC :

Colorectal cancer

LCM :

Laser capture microdissection

PAGE :

Polyacrylamide gel electrophoresis

References

  • Bowden ET, Barth M, Thomas D, Glazer RI, Mueller SC (1999) An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation. Oncogene 18:4440–4449

    Article  PubMed  CAS  Google Scholar 

  • Brattain MG, Fine WD, Khaled FM, Thompson J, Brattain DE (1981) Heterogeneity of malignant cells from a human colonic carcinoma. Cancer Res 41:1751–1756

    PubMed  CAS  Google Scholar 

  • Campbell DH, Sutherland RL, Daly RJ (1999) Signaling pathways and structural domains required for phosphorylation of EMS1/cortactin. Cancer Res 59:5376–5385

    PubMed  CAS  Google Scholar 

  • Cunningham CC (1992) Actin structural proteins in cell motility. Cancer Metastasis Rev 11:69–77

    Article  PubMed  CAS  Google Scholar 

  • Diep CB, Parada LA, Teixeira MR, Eknaes M, Nesland JM, Johansson B, Lothe RA (2003) Genetic profiling of colorectal cancer liver metastases by combined comparative genomic hybridization and G-banding analysis. Genes Chromosomes Cancer 36:189–197

    Article  PubMed  CAS  Google Scholar 

  • Fantl V, Smith R, Brookes S, Dickson C, Peters G (1993) Chromosome 11q13 abnormalities in human breast cancer. Cancer Surv 18:77–94

    PubMed  CAS  Google Scholar 

  • He QJ, Zeng WF, Sham JS, Xie D, Yang XW, Lin HL, Zhan WH, Lin F, Zeng SD, Nie D, Ma LF, Li CJ, Lu S, Guan XY (2003) Recurrent genetic alterations in 26 colorectal carcinomas and 21 adenomas from Chinese patients. Cancer Genet Cytogenet 144:112–118

    Article  PubMed  CAS  Google Scholar 

  • Huang C, Liu J, Haudenschild CC, Zhan X (1998) The role of tyrosine phosphorylation of cortactin in the locomotion of endothelial cells. J Biol Chem 273:25770–25776

    Article  PubMed  CAS  Google Scholar 

  • Huang C, Ni Y, Wang T, Gao Y, Haudenschild CC, Zhan X (1997) Down-regulation of the filamentous actin cross-linking activity of cortactin by Src-mediated tyrosine phosphorylation. J Biol Chem 272:13911–13915

    Article  PubMed  CAS  Google Scholar 

  • Knosel T, Petersen S, Schwabe H, Schluns K, Stein U, Schlag PM, Dietel M, Petersen I (2002) Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases. Virchows Arch 440:187–194

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Tondravi M, Liu J, Smith E, Haudenschild CC, Kaczmarek M, Zhan X (2001) Cortactin potentiates bone metastasis of breast cancer cells. Cancer Res 61:6906–6911

    PubMed  CAS  Google Scholar 

  • Lynch DK, Winata SC, Lyons RJ, Hughes WE, Lehrbach GM, Wasinger V, Corthals G, Cordwell S, Daly RJ (2003) A Cortactin-CD2-associated protein (CD2AP) complex provides a novel link between epidermal growth factor receptor endocytosis and the actin cytoskeleton. J Biol Chem 278:21805–21813

    Article  PubMed  CAS  Google Scholar 

  • Mayer R (1996) Gastrointestinal cancer. In: Dale DC, Federman DD (eds) Scientific American Medicine, vol 3. Scientific American, Inc., New York, pp 1–22

  • Meredith SD, Levine PA, Burns JA, Gaffey MJ, Boyd JC, Weiss LM, Erickson NL, Williams ME (1995) Chromosome 11q13 amplification in head and neck squamous cell carcinoma. Association with poor prognosis. Arch Otolaryngol Head Neck Surg 121:790–794

    PubMed  CAS  Google Scholar 

  • Patel AS, Schechter GL, Wasilenko WJ, Somers KD (1998) Overexpression of EMS1/cortactin in NIH3T3 fibroblasts causes increased cell motility and invasion in vitro. Oncogene 16:3227–3232

    Article  PubMed  CAS  Google Scholar 

  • Peters G, Fantl V, Smith R, Brookes S, Dickson C (1995) Chromosome 11q13 markers and D-type cyclins in breast cancer. Breast Cancer Res Treat 33:125–135

    Article  PubMed  CAS  Google Scholar 

  • Rinnerthaler G, Geiger B, Small JV (1988) Contact formation during fibroblast locomotion: involvement of membrane ruffles and microtubules. J Cell Biol 106:747–760

    Article  PubMed  CAS  Google Scholar 

  • Schuuring E, Verhoeven E, Mooi WJ, Michalides RJ (1992a) Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene 7:355–361

    PubMed  CAS  Google Scholar 

  • Schuuring E, Verhoeven E, van Tinteren H, Peterse JL, Nunnink B, Thunnissen FB, Devilee P, Cornelisse CJ, van de Vijver MJ, Mooi WJ, et al (1992b) Amplification of genes within the chromosome 11q13 region is indicative of poor prognosis in patients with operable breast cancer. Cancer Res 52:5229–5234

    PubMed  CAS  Google Scholar 

  • Tompkins WA, Watrach AM, Schmale JD, Schultz RM, Harris JA (1974) Cultural and antigenic properties of newly established cell strains derived from adenocarcinomas of the human colon and rectum. J Natl Cancer Inst 52:1101–1110

    PubMed  CAS  Google Scholar 

  • van Damme H, Brok H, Schuuring-Scholtes E, Schuuring E (1997) The redistribution of cortactin into cell-matrix contact sites in human carcinoma cells with 11q13 amplification is associated with both overexpression and post-translational modification. J Biol Chem 272:7374–7380

    Article  PubMed  Google Scholar 

  • Voura EB, Sandig M, Kalnins VI, Siu C (1998) Cell shape changes and cytoskeleton reorganization during transendothelial migration of human melanoma cells. Cell Tissue Res 293:375–387

    Article  PubMed  CAS  Google Scholar 

  • Weed SA, Karginov AV, Schafer DA, Weaver AM, Kinley AW, Cooper JA, Parsons JT (2000) Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex. J Cell Biol 151:29–40

    Article  PubMed  CAS  Google Scholar 

  • Weed SA, Parsons JT (2001) Cortactin: coupling membrane dynamics to cortical actin assembly. Oncogene 20:6418–6434

    Article  PubMed  CAS  Google Scholar 

  • Williams ME, Gaffey MJ, Weiss LM, Wilczynski SP, Schuuring E, Levine PA (1993) Chromosome 11Q13 amplification in head and neck squamous cell carcinoma. Arch. Otolaryngol. Head Neck Surg 119:1238–1243

    PubMed  CAS  Google Scholar 

  • Winawer SJ, St John DJ, Bond JH, Rozen P, Burt RW, Waye JD, Kronborg O, O’Brien MJ, Bishop DT, Kurtz RC, et al (1995) Prevention of colorectal cancer: guidelines based on new data. WHO Collaborating Center for the Prevention of Colorectal Cancer. Bull World Health Organ 73:7–10

    PubMed  CAS  Google Scholar 

  • Wu H, Parsons JT (1993) Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex. J Cell Biol 120:1417–1426

    Article  PubMed  CAS  Google Scholar 

  • Wu H, Reynolds AB, Kanner SB, Vines RR, Parsons JT (1991) Identification and characterization of a novel cytoskeleton-associated pp60src substrate. Mol Cell Biol 11:5113–5124

    PubMed  CAS  Google Scholar 

  • Yuan BZ, Zhou X, Zimonjic DB, Durkin ME, Popescu NC (2003) Amplification and overexpression of the EMS 1 oncogene, a possible prognostic marker, in human hepatocellular carcinoma. J Mol Diagn 5:48–53

    PubMed  CAS  Google Scholar 

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Acknowledgements

Grant support: This study was supported by National Natural Science Foundation of China (No. 30340085) and “211 project” of Education Ministry of China (526).

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Authors and Affiliations

  1. Beijing Cancer Hospital, Beijing Institute for Cancer Research, Peking University School of Oncology, Beijing, 100034, China

    Lian-Hai Zhang, Wen-Mei Li, Hui Ren & Jia-Fu Ji

  2. Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China

    Bo Tian

  3. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Li-Rong Diao & Bian-Hong Zhang

  4. Institute of Oncology & Zhongnan Hospital, Wuhan University, Wuhan, China

    Yong-Yan Xiong, Su-Fang Tian & Yan Li

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  1. Lian-Hai Zhang
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  2. Bo Tian
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  3. Li-Rong Diao
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  7. Wen-Mei Li
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  9. Yan Li
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  10. Jia-Fu Ji
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Correspondence to Jia-Fu Ji.

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Y. Li is co-corresponding author

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Zhang, LH., Tian, B., Diao, LR. et al. Dominant expression of 85-kDa form of cortactin in colorectal cancer. J Cancer Res Clin Oncol 132, 113–120 (2006). https://doi.org/10.1007/s00432-005-0046-8

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  • DOI: https://doi.org/10.1007/s00432-005-0046-8

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