The functions and regulations of DAPK in cancer metastasis
The functions and regulations of DAPK in cancer metastasis
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DOI：
10.1007/s10495-013-0923-6
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发表时间：
2014-02-01
期刊：
影响因子：
7.2
通讯作者：
Chen, Ruey-Hwa
中科院分区：
文献类型：
--
作者：
Chen, Hsin-Yi;Lee, Yu-Ru;Chen, Ruey-Hwa
转移是大多数癌症死亡的原因，但它仍然是一个知之甚少的过程。最近有证据表明，死亡相关蛋白激酶（DAPK）是一种潜在的转移抑制因子。在许多转移性癌症中，通过表观遗传、转录、转录后或翻译后机制观察到DAPK下调或失活。在某些情况下，DAPK下调与转移性复发相关。动物研究进一步表明，DAPK可以抑制早期和晚期转移过程，这表明DAPK具有多种抑制转移的机制。基于细胞的研究表明，DAPK介导多种类型的细胞死亡，包括凋亡、自噬性死亡和坏死，这取决于死亡刺激和细胞环境。DAPK还调节细胞骨架蛋白介导死亡相关的细胞形态学改变和抑制细胞运动。除肿瘤细胞外，DAPK还可影响基质细胞，调节基质细胞的生存和功能。这些影响可能都有助于抑制DAPK的转移作用。本文就DAPK抗转移作用的分子机制作一综述。
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.