The functions and regulations of DAPK in cancer metastasis

Hsin Yi Chen, Yu Ru Lee, Ruey Hwa Chen

Research output: Contribution to journalReview articlepeer-review

42 Citations (Scopus)

Abstract

Metastasis is responsible for most cancer deaths but it remains a poorly understood process. Recent evidence has emerged that death-associated protein kinase (DAPK) is a candidate of metastasis suppressor. DAPK downregulation or inactivation has been observed in a number of metastatic cancers through epigenetic, transcriptional, post-transcriptional, or post-translational mechanism. In certain cases, DAPK downregulation correlates with metastatic recurrence. Animal studies further show that DAPK impedes both early-stage and late-stage metastatic process, which suggests that DAPK possesses multiple mechanisms to suppress metastasis. Cell-based studies revealed that DAPK mediates several types of cell death, including apoptosis, autophagic death and necrosis, depending on death stimuli and cell context. DAPK also regulates cytoskeleton proteins to mediate death-associated cell morphological alterations and to inhibit cell motility. Besides tumor cells, DAPK can influence on stromal cells to regulate their survival and functions. These effects likely all contribute to the metastasis suppressive role of DAPK. The detail molecular mechanisms of these anti-metastatic effects of DAPK are reviewed in this article.

Original languageEnglish
Pages (from-to)364-370
Number of pages7
JournalApoptosis
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • Cancer metastasis
  • Cell death
  • Cell motility
  • DAPK
  • Tumor suppressor

ASJC Scopus subject areas

  • Biochemistry, medical
  • Cancer Research
  • Clinical Biochemistry
  • Cell Biology
  • Pharmacology
  • Pharmaceutical Science

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