Skip to main content

The Tight Junction, Intercellular Seal as a Cell Signaling Player: Protocols for Examination of Its Status

  • Protocol
  • First Online:
Claudins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 762))

  • 2111 Accesses

Abstract

Tight junctions (TJs) are intercellular structures in epithelial and endothelial cells, primarily playing ­critical roles in cell–cell adhesion. Among their molecular components, claudins are the main constituents as integral membrane proteins, encoded by at least 24 members of a single gene family. Accumulated ­evidence has demonstrated that TJ proteins such as claudins are directly involved in the regulation of ­cellular functions such as proliferation, differentiation, and apoptosis, due to their ability to recruit various signaling molecules that have proliferative and differentiative capacities, including transcription factors, lipid phosphatases, and cell cycle regulators. It is thus clear that TJs are not simple static constituents to establish cell adhesion structures, rather also functioning in cell signaling component that has functions in receiving environmental cues and transmitting signals inside the cells.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tsukita, S., Furuse, M., and Itoh, M. (2001) Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2, 285–293.

    Article  PubMed  CAS  Google Scholar 

  2. Matter, K., and Balda, M.S. (2003) Signalling to and from tight junctions. Nat Rev Mol Cell Biol 4, 225–236.

    Article  PubMed  CAS  Google Scholar 

  3. Matter, K., Aijaz, S., Tsapara, A., and Balda, M.S. (2005) Mammalian tight junctions in the regulation of epithelial differentiation and proliferation. Curr Opin Cell Biol 17, 453–458.

    Article  PubMed  CAS  Google Scholar 

  4. Furuse, M., Hirase, T. Itoh, M., Nagafuchi, A., Yonemura, S., and Tsukita, S. (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123, 1777–1788.

    Article  PubMed  CAS  Google Scholar 

  5. Saitou, M., Furuse, M., Sasaki, H., Schulzke, J.D., Fromm, M., Takano, H., et al. (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11, 4131–4142.

    PubMed  CAS  Google Scholar 

  6. Sawada, N., Murata, M., Kikuchi, K., Osanai, M., Tobioka, H., Kojima, T., et al. (2003) Tight junctions and human diseases. Med Electron Microsc 36, 147–156.

    Article  PubMed  Google Scholar 

  7. Osanai, M., Murata, M., Nishikiori, N., Chiba, H., Kojima, T., and Sawada, N. (2006) Epigenetic silencing of occludin promotes tumorigenic and metastatic properties of ­cancer cells via modulations of unique sets of apoptosis-associated genes. Cancer Res 66, 9125–9133.

    Article  PubMed  CAS  Google Scholar 

  8. Osanai, M., Murata, M., Nishikiori, N., Chiba, H., Kojima, T., and Sawada, N. (2007) Occludin-mediated premature senescence is a fail-safe mechanism against tumorigenesis in breast carcinoma cells. Cancer Sci 98, 1027–1034.

    Article  PubMed  CAS  Google Scholar 

  9. Osanai, M., Murata, M., Chiba, H., Kojima, T., and Sawada, N. (2007) Epigenetic silencing of claudin-6 promotes anchorage-independent growth of breast carcinoma cells. Cancer Sci 98, 1557–1562.

    Article  PubMed  CAS  Google Scholar 

  10. Osanai, M. (2007) Tight junctions and cancer development, Encyclopedia of Cancer. M. Schwab. Springer.

    Google Scholar 

  11. Morin, P.J. (2005) Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 65, 9603–9606.

    Article  PubMed  CAS  Google Scholar 

  12. Michl, P., Barth, C., Buchholz, M., Lerch, M.M., Rolke, M., Holzmann, K.H. et al. (2003) Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res 63, 6265–6271.

    PubMed  CAS  Google Scholar 

  13. Hoevel, T., Macek, R., Swisshelm, K., and Kubbies, M. (2004) Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids. Int J Cancer 108, 374–383.

    Article  PubMed  CAS  Google Scholar 

  14. Tobioka, H., Isomura, H., Kokai, Y., Tokunaga, Y., Yamaguchi, J., and Sawada, N. (2004) Occludin expression decreases with the progression of human endometrial carcinoma. Hum Pathol 35, 159–164.

    Article  PubMed  CAS  Google Scholar 

  15. Li, D., and Mrsny, R.J. (2000) Oncogenic Raf-1 disrupts epithelial tight junctions via downregulation of occludin. J Cell Biol 148, 791–800.

    Article  PubMed  CAS  Google Scholar 

  16. Tokes, A.M., Kulka, J., Paku, S., Szik, A., Paska, C., Novak, P.K., et al. (2005) Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res 7, R296–305.

    Article  PubMed  CAS  Google Scholar 

  17. Resnick, M.B., Konkin, T., Routhier, J., Sabo, E., and Pricolo, V.E. (2005) Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study. Mod Pathol 18, 511–518.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Makoto Osanai .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Osanai, M. (2011). The Tight Junction, Intercellular Seal as a Cell Signaling Player: Protocols for Examination of Its Status. In: Turksen, K. (eds) Claudins. Methods in Molecular Biology, vol 762. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-185-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-185-7_4

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-184-0

  • Online ISBN: 978-1-61779-185-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics