Journal Article

Desmoplakin acts as a tumor suppressor by inhibition of the Wnt/β-catenin signaling pathway in human lung cancer

Linlin Yang, Yuan Chen, Tiantian Cui, Thomas Knösel, Qing Zhang, Kai Frederik Albring, Otmar Huber and Iver Petersen

in Carcinogenesis

Volume 33, issue 10, pages 1863-1870
Published in print October 2012 | ISSN: 0143-3334
Published online July 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs226
Desmoplakin acts as a tumor suppressor by inhibition of the Wnt/β-catenin signaling pathway in human lung cancer

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Desmosomes are intercellular junctions that confer strong cell–cell adhesion, thus conferring resistance against mechanical stress on epithelial tissues. A body of evidence indicates that decreased expression of desmosomal proteins is associated with poor prognosis in various cancers. As a key component of desmosomal plaque proteins, the functional role of desmoplakin (DSP) in cancer is not yet elucidated. Here, we reported the anti-tumorigenic activity of DSP in non-small cell lung cancer (NSCLC). We found by DSP DNA methylation that DSP expression was downregulated in 8 out of 11 lung cancer cell lines and in 34 out of 56 primary lung tumors . Ectopic expression of DSP in the NSCLC cell line H157 significantly inhibited cell proliferation, anchorage-independent growth, migration and invasion and also increased the sensitivity of NSCLC cells to apoptosis induced by an anticancer drug, gemcitabine. Furthermore, overexpression of DSP enhanced expression of plakoglobin (γ-catenin), resulting in decreased T-cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity and reduced expression of the Wnt/β-catenin target genes Axin2 and matrix metalloproteinase MMP14. In accordance, DSP suppression by small interfering RNA resulted in downregulation of plakoglobin and upregulation of β-catenin and MMP14. Taken together, these data suggest that DSP is inactivated in lung cancer by an epigenetic mechanism, increases the sensitivity to anticancer drug-induced apoptosis and has tumor-suppressive function, possibly through inhibition of the Wnt/β-catenin signaling pathway in NSCLC cells. The epigenetic regulation of DSP and its ability to increase the sensitivity to anticancer drug-induced apoptosis has potential implications for clinical application.

Journal Article.  5603 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.