Role of TGF-β-induced Claudin-4 expression through c-Jun signaling in non-small cell lung cancer

Girish Rachakonda, Trung Vu, Lin Jin, Debangshu Samanta, Pran K. Datta

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Claudin-4 has been identified as an integral member of tight junctions and has been found to be upregulated in various types of cancers especially in metastatic cancers. However, the molecular mechanism of the upregulation of Claudin-4 and its role in lung tumorigenesis are unknown. The aim of the present study is to investigate the role of Claudin-4 on migration and tumorigenicity of lung cancer cells and to examine the regulatory effects of TGF-β on Claudin-4 expression. We have observed that TGF-β induces the expression of Claudin-4 dramatically in lung cell lines in a time dependent manner. TGF-β-induced Smad signaling is important for enhancing Claudin-4 mRNA level through inducing its promoter activity. Treatment with curcumin, a c-Jun inhibitor, or stable knockdown of c-Jun abrogates TGF-β-induced Claudin-4 expression suggesting an involvement of the c-Jun pathway. Notably, TGF-β-induced Claudin-4 expression through c-Jun pathway plays a role in TGF-β-mediated motility and tumorigenicity of these cells. In support of these observations, we have uncovered that Claudin-4 is upregulated in 14 of 24 (58%) lung tumors when compared with normal lung tissue. This is the first study to show how TGF-β regulates the expression of Claudin-4 through c-Jun signaling and how this pathway contributes to the migratory and tumorigenic phenotype of lung tumor cells.

Original languageEnglish (US)
Pages (from-to)1537-1544
Number of pages8
JournalCellular Signalling
Issue number10
StatePublished - Oct 1 2016
Externally publishedYes


  • Claudin-4
  • Migration
  • Smad
  • TGF-β
  • Tumorigenicity
  • c-Jun

ASJC Scopus subject areas

  • Cell Biology


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