The interaction between the Wnt/β-catenin signaling cascade and PKG activation in cancer.
The interaction between the Wnt/β-catenin signaling cascade and PKG activation in cancer.
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DOI：
10.7555/jbr.31.20160133
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发表时间：
2017-01-19
影响因子：
2.3
通讯作者：
A Piazza G
中科院分区：
文献类型：
--
作者：
Lee K;A Piazza G
Wnt/β-连环蛋白信号级联的激活在结直肠癌（CRC）中已经得到充分研究和记录。大量流行病学研究表明，长期使用非甾体抗炎药（NSAID）可降低CRC的发病率和死亡风险。据报道，NSAID舒林酸还可导致家族性腺瘤性息肉病患者的癌前腺瘤消退，这些患者具有发展为CRC的高风险。非甾体抗炎药的癌症化学预防活性的机制尚不清楚，但可能与其环氧合酶抑制活性无关。新出现的证据表明，舒林酸通过升高第二信使环磷酸鸟苷（cGMP），抑制某些磷酸二酯酶同工酶激活cGMP依赖性蛋白激酶（PKG）的活性，从而抑制结肠肿瘤细胞的生长。PKG激活已显示抑制β-连环蛋白的核转位，降低β-连环蛋白mRNA和蛋白水平，并抑制β-连环蛋白的转录活性。本文综述了Wnt/β-catenin信号级联反应通过抑制PDE和升高细胞内cGMP水平与PKG活化之间的关系。
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity. Emerging evidence suggests that sulindac inhibits the growth of colon tumor cells by suppressing the activity of certain phosphodiesterase isozymes to activate cGMP-dependent protein kinase, PKG, through the elevation of the second messenger cyclic guanosine monophosphote, cGMP. PKG activation has been shown to inhibit the nuclear translocation of β-catenin, reduce β-catenin mRNA and protein levels, and suppress the transcriptional activity of β-catenin. This review describes the relationship between the Wnt/β-catenin signaling cascade and the activation of PKG through PDE inhibition and elevation of intracellular cGMP levels.