Epigenetic activation of human kallikrein 13 enhances malignancy of lung adenocarcinoma by promoting N-cadherin expression and laminin degradation

Ruey Hwang Chou*, Sheng Chieh Lin, Hui Chin Wen, Cheng-Wen Wu, Wun Shaing Wayne Chang

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The tissue kallikrein (KLK) family contains 15 genes (KLK1-. KLK15) tandemly arranged on chromosome 19q13.4 that forms the largest cluster of contiguous protease genes in the human genome. Here, we provide mechanistic evidence showing that the expression of KLK13, one of the most recently identified family members, is significantly up-regulated in metastatic lung adenocarcinoma. Whilst overexpression of KLK13 resulted in an increase in malignant cell behavior, knockdown of its endogenous gene expression caused a significant decrease in cell migratory and invasive properties. Functional studies further demonstrated that KLK13 is activated via demethylation of its upstream region. The elevated KLK13 protein then enhances the ability of tumor cells to degrade extracellular laminin that, subsequently, facilitates cell metastatic potential in the in vivo SCID mouse xenograft model. KLK13 was also found to induce the expression of N-cadherin to help promote tumor cell motility. Together, these results reveal the enhancing effects of KLK13 on tumor cell invasion and migration, and that it may serve as a diagnostic/prognostic marker and a potential therapeutic target for lung cancer.

Original languageEnglish
Pages (from-to)442-447
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume409
Issue number3
DOIs
StatePublished - 10 Jun 2011

Keywords

  • CpG methylation
  • Invasion
  • Kallikrein
  • Lung cancer
  • Migration

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