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The functions and regulations of DAPK in cancer metastasis

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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.

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Abbreviations

CRC:

Colorectal carcinoma

DAPK:

Death-associated protein kinase

miRNA:

MicroRNA

MK:

Megakaryocyte

MLCII:

Regulatory light chain of myosin II

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Acknowledgments

This work is supported by National Science Council Frontier Grant 101-2321-B-001-007.

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Authors and Affiliations

  1. Graduate Institute of Cancer Biology & Drug Discovery, College of Medical Science & Technology, Taipei Medical University, Taipei, Taiwan

    Hsin-Yi Chen

  2. Institute of Biological Chemistry, Academia Sinica, 128 Academia Rd., Sec II, Nankang, Taipei, 115, Taiwan

    Yu-Ru Lee & Ruey-Hwa Chen

  3. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan

    Ruey-Hwa Chen

  4. Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

    Ruey-Hwa Chen

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  1. Hsin-Yi Chen
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Correspondence to Ruey-Hwa Chen.

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Chen, HY., Lee, YR. & Chen, RH. The functions and regulations of DAPK in cancer metastasis. Apoptosis 19, 364–370 (2014). https://doi.org/10.1007/s10495-013-0923-6

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