Skip to main content

Advertisement

SpringerLink
Log in

High expression of CASK correlates with progression and poor prognosis of colorectal cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

Calcium/calmodulin-dependent serine protein kinase (CASK), which localizes at cell–cell adhesion sites and binds to the heparan sulfate proteoglycan syndecan-2, is involved in cell proliferation, cytoskeletal remodeling, and cell migration. To demonstrate the role of CASK in colorectal cancer (CRC) carcinogenesis, we examined the expression of CASK and its binding protein syndecan-2 in human CRC tissues. The expression of CASK was measured in CRC specimens and the controls from adenomas and normal mucosae by immunohistochemical staining and Western blot analysis. Syndecan-2 protein level was tested in CRC samples and the controls by Western blot analysis. The correlations between CASK expression and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analyzed. Compared to the controls, both CASK and syndecan-2 expression were enhanced in CRC tissues. Furthermore, high expression of CASK and syndecan-2 was significantly correlated with advanced tumor stage, lymphatic invasion, lymph node metastasis, vascular invasion, liver metastasis, and unresectable metastatic CRC. Survival analysis showed that patients with low CASK staining had a significantly better survival compared to patients with high CASK staining. In multivariate analysis, CASK overexpression, advanced tumor stage, lymph node metastasis, vasvular invasion, and liver metastasis were independent prognostic factors of poor DFS and OS. Our present study indicates that CASK overexpression is associated with an unfavorable prognosis. CASK is an independent prognostic factor for CRC, which suggests that it is a novel and crucial predictor for CRC metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Reference

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.

    Article  PubMed  Google Scholar 

  2. Kraus S, Nabiochtchikov I, Shapira S, Arber N. Recent advances in personalized colorectal cancer research. Cancer Lett. 2014;347:15–21.

    Article  CAS  PubMed  Google Scholar 

  3. Martin-Belmonte F, Perez-Moreno M. Epithelial cell polarity, stem cells and cancer. Nat Rev Cancer. 2012;12:23–38.

    CAS  Google Scholar 

  4. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9:265–73.

    Article  CAS  PubMed  Google Scholar 

  5. Parsons JT, Horwitz AR, Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol. 2010;11:633–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med. 2009;361:2449–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Wu ZQ, Brabletz T, Fearon E, Willis AL, Hu CY, Li XY, et al. Canonical wnt suppressor, axin2, promotes colon carcinoma oncogenic activity. Proc Natl Acad Sci U S A. 2012;109:11312–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Hata Y, Butz S, Sudhof TC. Cask: A novel dlg/psd95 homolog with an n-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J Neurosci. 1996;16:2488–94.

    CAS  PubMed  Google Scholar 

  9. Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali ET, et al. Syncam, a synaptic adhesion molecule that drives synapse assembly. Science. 2002;297:1525–31.

    Article  CAS  PubMed  Google Scholar 

  10. Cohen AR, Woods DF, Marfatia SM, Walther Z, Chishti AH, Anderson JM. Human cask/lin-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells. J Cell Biol. 1998;142:129–38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Kwon MJ, Kim Y, Choi Y, Kim SH, Park S, Han I, et al. The extracellular domain of syndecan-2 regulates the interaction of hct116 human colon carcinoma cells with fibronectin. Biochem Biophys Res Commun. 2013;431:415–20.

    Article  CAS  PubMed  Google Scholar 

  12. Park H, Kim Y, Lim Y, Han I, Oh ES. Syndecan-2 mediates adhesion and proliferation of colon carcinoma cells. J Biol Chem. 2002;277:29730–6.

    Article  CAS  PubMed  Google Scholar 

  13. Ryu HY, Lee J, Yang S, Park H, Choi S, Jung KC, et al. Syndecan-2 functions as a docking receptor for pro-matrix metalloproteinase-7 in human colon cancer cells. J Biol Chem. 2009;284:35692–701.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Martinez-Estrada OM, Villa A, Breviario F, Orsenigo F, Dejana E, Bazzoni G. Association of junctional adhesion molecule with calcium/calmodulin-dependent serine protein kinase (cask/lin-2) in human epithelial caco-2 cells. J Biol Chem. 2001;276:9291–6.

    Article  CAS  PubMed  Google Scholar 

  15. Coussen F, Normand E, Marchal C, Costet P, Choquet D, Lambert M, et al. Recruitment of the kainate receptor subunit glutamate receptor 6 by cadherin/catenin complexes. J Neurosci. 2002;22:6426–36.

    CAS  PubMed  Google Scholar 

  16. Weigand JE, Boeckel JN, Gellert P, Dimmeler S. Hypoxia-induced alternative splicing in endothelial cells. PLoS One. 2012;7:e42697.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Caruana G. Genetic studies define maguk proteins as regulators of epithelial cell polarity. Int J Dev Biol. 2002;46:511–8.

    CAS  PubMed  Google Scholar 

  18. Funke L, Dakoji S, Bredt DS. Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions. Annu Rev Biochem. 2005;74:219–45.

    Article  CAS  PubMed  Google Scholar 

  19. Qi J, Su Y, Sun R, Zhang F, Luo X, Yang Z. Cask inhibits ecv304 cell growth and interacts with id1. Biochem Biophys Res Commun. 2005;328:517–21.

    Article  CAS  PubMed  Google Scholar 

  20. Hsueh YP, Wang TF, Yang FC, Sheng M. Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase cask/lin-2. Nature. 2000;404:298–302.

    Article  CAS  PubMed  Google Scholar 

  21. Gold KA, Kim ES, Liu D, Yuan P, Behrens C, Solis Soto LM et al. Prediction of survival in resected non-small cell lung cancer using a protein-expression based risk model: implications for personalized chemoprevention and therapy. Clin Cancer Res. 2014;20:1946–54.

  22. Wang Q, Lu J, Yang C, Wang X, Cheng L, Hu G, et al. Cask and its target gene reelin were co-upregulated in human esophageal carcinoma. Cancer Lett. 2002;179:71–7.

    Article  CAS  PubMed  Google Scholar 

  23. Rohrbeck A, Neukirchen J, Rosskopf M, Pardillos GG, Geddert H, Schwalen A, et al. Gene expression profiling for molecular distinction and characterization of laser captured primary lung cancers. J Transl Med. 2008;6:69.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Au CW, Siu MK, Liao X, Wong ES, Ngan HY, Tam KF, et al. Tyrosine kinase b receptor and bdnf expression in ovarian cancers—effect on cell migration, angiogenesis and clinical outcome. Cancer Lett. 2009;281:151–61.

    Article  CAS  PubMed  Google Scholar 

  25. Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001;93:266–76.

    Article  CAS  PubMed  Google Scholar 

  26. Yilmaz M, Christofori G. Emt, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009;28:15–33.

    Article  PubMed  Google Scholar 

  27. Beauvais DM, Rapraeger AC. Syndecans in tumor cell adhesion and signaling. Reprod Biol Endocrinol. 2004;2:3.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Contreras HR, Fabre M, Granes F, Casaroli-Marano R, Rocamora N, Herreros AG, et al. Syndecan-2 expression in colorectal cancer-derived ht-29 m6 epithelial cells induces a migratory phenotype. Biochem Biophys Res Commun. 2001;286:742–51.

    Article  CAS  PubMed  Google Scholar 

  29. Yamaguchi H, Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta. 2007;1773:642–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Hsueh YP, Yang FC, Kharazia V, Naisbitt S, Cohen AR, Weinberg RJ, et al. Direct interaction of cask/lin-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses. J Cell Biol. 1998;142:139–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation Of China (No. 81172295). The authors sincerely thank the patients and their families for their participation in this study.

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China

    Jin-Lai Wei, Zhong-Xue Fu, Jin-Bao Guo, Wei-Dong Lu & Hao Wang

  2. Department of Emergency and Intensive Care Unit, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China

    Min Fang

  3. Department of pathology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200080, China

    Qiu-Yuan Zhou

  4. Department of pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Qing-Ning Zhao

Authors
  1. Jin-Lai Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhong-Xue Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qiu-Yuan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing-Ning Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin-Bao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei-Dong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhong-Xue Fu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, JL., Fu, ZX., Fang, M. et al. High expression of CASK correlates with progression and poor prognosis of colorectal cancer. Tumor Biol. 35, 9185–9194 (2014). https://doi.org/10.1007/s13277-014-2179-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2179-3

Keywords

Search

Navigation