Involvement of the MEK/ERK pathway in EGF-induced E-cadherin down-regulation

Etsu Tashiro, Shizuka Henmi, Hiroyuki Odake, Seitaro Ino, Masaya Imoto

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

E-cadherin is a major component of the epithelial adherens junction. However, the regulatory mechanism of E-cadherin expression is still poorly understood. In this study, we found that EGF decreased E-cadherin expression at both mRNA and protein levels in colorectal carcinoma LoVo cells. Since E-cadherin down-regulation is a well-known hallmark of the EMT (Epithelial-Mesenchymal Transition), we investigated whether EGF induced E-cadherin down-regulation during the EMT. EGF was unable to affect the expression of mesenchymal markers (such as N-cadherin, vimentin or fibronectin) or EMT-regulating transcription factors (such as SNAIL, SLUG, ZEB1, ZEB2 or TWIST), suggesting that EGF induced E-cadherin down-regulation via an EMT-independent mechanism. On the other hand, the MEK inhibitor U0126 was found to suppress EGF-induced E-cadherin down-regulation at the transcriptional level, suggesting that the MEK/ERK pathway is involved in EGF-induced E-cadherin down-regulation. Moreover, we also found that EGF disrupted cell-cell contact, stimulated cells to form an elongated shape with filamentous protrusions, and induced cell migration in LoVo cells. These effects were suppressed by U0126. Therefore, EGF is suggested to induce E-cadherin down-regulation at the transcriptional level through the MEK/ERK pathway, which might result in, at least in part, the induction of cellular morphological changes and cell migration in LoVo cells.

Original languageEnglish
Pages (from-to)801-806
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume477
Issue number4
DOIs
Publication statusPublished - 2016 Sep 2

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MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Cadherins
Epidermal Growth Factor
Down-Regulation
Epithelial-Mesenchymal Transition
Cell Movement
Adherens Junctions
Vimentin
Fibronectins
Colorectal Neoplasms
Transcription Factors
Messenger RNA

Keywords

  • E-cadherin
  • EGF
  • EMT
  • ERK
  • JNK

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Involvement of the MEK/ERK pathway in EGF-induced E-cadherin down-regulation. / Tashiro, Etsu; Henmi, Shizuka; Odake, Hiroyuki; Ino, Seitaro; Imoto, Masaya.

In: Biochemical and Biophysical Research Communications, Vol. 477, No. 4, 02.09.2016, p. 801-806.

Research output: Contribution to journalArticle

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