Ligand independent aryl hydrocarbon receptor inhibits lung cancer cell invasion by degradation of Smad4

Chen Chen Lee, Wen Hao Yang, Ching Hao Li, Yu Wen Cheng, Chi Hao Tsai, Jaw Jou Kang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Although AhR plays a crucial role in air toxicant-induced carcinogenesis, AhR expression was shown to negatively regulate tumorigenesis. Therefore, in the present study, we investigated the effect of AhR without ligand treatment on cancer invasion in lung cancer cell lines. Lung cancer cells expressing lower levels of AhR showed higher invasion ability (H1299 cells) compared with cells expressing higher levels of AhR (A549 cells). Overexpression of AhR in H1299 cells inhibited the invasion ability. We found that vimentin expression was inhibited in AhR-overexpressing H1299 cells. Additionally, the expression of EMT-related transcriptional factors Snail and ID-1 decreased. Interestingly, we found that Smad4 degradation was induced in AhR-overexpressing H1299 cells. Our data showed that AhR could interact with Jun-activation domain binding protein (Jab1) and Smad4, which may cause degradation of Smad4 by the proteasome. Our data suggest that AhR affects the transforming growth factor-β signaling pathway by inducing Smad4 degradation by the proteasome and suppressing tumor metastasis via epithelial to mesenchymal transition reduction in lung cancer cells.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalCancer Letters
Volume376
Issue number2
DOIs
Publication statusPublished - Jul 1 2016

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Aryl Hydrocarbon Receptors
Lung Neoplasms
Ligands
Proteasome Endopeptidase Complex
Carcinogenesis
Epithelial-Mesenchymal Transition
Transforming Growth Factors
Vimentin
Xenobiotics
Neoplasms
Carrier Proteins
Air

Keywords

  • Aryl hydrocarbon receptor
  • Epithelial to mesenchymal transition
  • Jun-activation domain binding protein
  • Lung cancer
  • Smad4
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ligand independent aryl hydrocarbon receptor inhibits lung cancer cell invasion by degradation of Smad4. / Lee, Chen Chen; Yang, Wen Hao; Li, Ching Hao; Cheng, Yu Wen; Tsai, Chi Hao; Kang, Jaw Jou.

In: Cancer Letters, Vol. 376, No. 2, 01.07.2016, p. 211-217.

Research output: Contribution to journalArticle

Lee, Chen Chen ; Yang, Wen Hao ; Li, Ching Hao ; Cheng, Yu Wen ; Tsai, Chi Hao ; Kang, Jaw Jou. / Ligand independent aryl hydrocarbon receptor inhibits lung cancer cell invasion by degradation of Smad4. In: Cancer Letters. 2016 ; Vol. 376, No. 2. pp. 211-217.
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