Salt-inducible kinase 1 regulates E-cadherin expression and intercellular junction stability

Kristina Eneling, Laura Brion, Vanda Pinto, Maria J. Pinho, Jacob I. Sznajder, Naoki Mochizuki, Kazuo Emoto, Patricio Soares-da-Silva, Alejandro M. Bertorello*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The protein kinase liver kinase B1 (LKB1) regulates cell polarity and intercellular junction stability. Also, LKB1 controls the activity of salt-inducible kinase 1 (SIK1). The role and relevance of SIK1 and its downstream effectors in linking the LKB1 signals within these processes are partially understood. We hypothesize that SIK1 may link LKB1 signals to the maintenance of epithelial junction stability by regulating E-cadherin expression. Results from our studies using a mouse lung alveolar epithelial (MLE-12) cell line or human renal proximal tubule (HK2) cell line transiently or stably lacking the expression of SIK1 (using SIK1 siRNAs or shRNAs), or with its expression abrogated (sik1+/+ vs. sik1-/-mice), indicate that suppression of SIK1 (∼40%) increases the expression of the transcriptional repressors Snail2 (∼12-fold), Zeb1 (∼100%), Zeb2 (∼50%), and TWIST (∼20-fold) by activating cAMP-response element binding protein. The lack of SIK1 and activation of transcriptional repressors decreases the availability of E-cadherin (mRNA and protein expression by ∼100 and 80%, respectively) and the stability of intercellular junctions in epithelia (decreases in transepithelial resistance). Furthermore, LKB1-mediated increases in E-cadherin expression are impaired in cells where SIK1 has been disabled. We conclude that SIK1 is a key regulator of E-cadherin expression, and thereby contributes to the stability of intercellular junctions.

Original languageEnglish (US)
Pages (from-to)3230-3239
Number of pages10
JournalFASEB Journal
Volume26
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • Epithelial polarity
  • Liver kinase B1
  • Metastatic transformation
  • Sodium transport
  • Transepithelial resistance
  • Vectorial transport

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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