Microtubule disruption in keratinocytes induces cell-cell adhesion through activation of endogenous E-cadherin

Sun-Ho Kee, P. M. Steinert

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The association of the cytoskeleton with the cadherin-catenin complex is essential for strong cell-cell adhesion in epithelial cells. In this study, we have investigated the effect of microtubule organization on cell-cell adhesion in differentiating keratinocytes. When microtubules of normal human epidermal keratinocytes (NHEKs) grown in low calcium media (0.05 mM) were disrupted with nocodazole or colcemid, cell-cell adhesion was induced through relocalization of the Ecadherin-catenin-actin complex to the cell periphery. This was accompanied by actin polymerization. Also, it was found that microtubule disruption-induced cell-cell adhesion was significantly reduced in more advanced differentiated keratinocytes. For example, when NHEK cells cultured under high calcium (1.2 mM) for 8 d and then in low calcium for 1 d were treated with nocodazole, there was no induction of cell-cell adhesion. Also long-term treatment of a phorbol ester for 48 h inhibited nocodazole-induced cell-cell adhesion of NHEK. Furthermore, this nocodazole-induced cell-cell adhesion could be observed in squamous cancer cell lines (A431 and SCC-5, -9, and -25) under low calcium condition, but not in the keratinocyte cell lines derived from normal epidermis (HaCaT, RHEK). On the other hand, HaCaT cells continuously cultivated in low calcium media regained a less differentiated phenotype such as decreased expression of cytokeratin 10, and increased K5; these changes were accompanied with inducibility of cell-cell adhesion by nocodazole. Together, our results suggest that microtubule disruption can induce the cell-cell adhesion via activation of endogenous E-cadherin in non- or early differentiating keratinocytes. However, this is no longer possible in advanced terminally differentiating keratinocytes, possibly due to irreversible changes effected by cell envelope barrier formation.

Original languageEnglish
Pages (from-to)1983-1993
Number of pages11
JournalMolecular Biology of the Cell
Volume12
Issue number7
Publication statusPublished - 2001 Nov 21
Externally publishedYes

Fingerprint

Cadherins
Keratinocytes
Cell Adhesion
Microtubules
Nocodazole
Calcium
Catenins
Actins
Demecolcine
Cell Line
Phorbol Esters
Keratins
Cytoskeleton
Epidermis
Polymerization
Cultured Cells
Epithelial Cells
Phenotype

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Microtubule disruption in keratinocytes induces cell-cell adhesion through activation of endogenous E-cadherin. / Kee, Sun-Ho; Steinert, P. M.

In: Molecular Biology of the Cell, Vol. 12, No. 7, 21.11.2001, p. 1983-1993.

Research output: Contribution to journalArticle

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