The interaction between the Wnt/β-catenin signaling cascade and PKG activation in cancer
Kevin Lee
Gary A Piazza
摘要：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,cGMR 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.
机标关键词：familial adenomatous polyposisnuclear translocationinhibitory activitycolorectal cancersecond messengerprotein kinasetumor cellsthe growth
分类号：R458(治疗学)
论文发表日期：2017-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 189-196 )
英文信息