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Muscarinic cholinergic signaling in cervical cancer cells affects cell motility via ERK1/2 signaling.

机译:子宫颈癌细胞中的毒蕈碱胆碱能信号传导通过ERK1 / 2信号传导影响细胞运动。

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The etiology of cervical cancer depends primarily on infection with human papillomaviruses, but tobacco smoking is the most important behavioral risk factor for this cancer. Therefore, we have previously confirmed involvement of nicotinic acetylcholine receptors (nAChRs) in cervical cancer biology. In order to comprehensively evaluate the role of cholinergic signaling in cervical cells, we have addressed additional participation of muscarinic acetylcholine receptors (mAChRs).We have studied the expression of mAChRs and cholinergic system components by reverse transcription PCR and Western blots, the motility of cervical cancer cells in cell culture, and the signaling from mAChRs via the ERK1/2 signaling pathway.The cervical cancer cells HeLa, SiHa and CaSki express four of the five mAChRs, M1, M3, M4, and M5, and the acetylcholine (ACh) synthesizing and degrading enzymes choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), and vesicular ACh transporter (VAChT). mAChR-dependent signaling induces cervical cell motility, which requires ERK1/2 activation, and could be abrogated by mAChR antagonists.The epidemiological finding that tobacco smoke raises the prevalence of cervical cancer has led to analysis of the cholinergic signaling in cervical biology and carcinogenesis. Cervical cancer cells express several nAChRs and mAChRs, whose activation leads to changes of cellular properties such as increased motility and proliferation that favor a carcinogenic phenotype. The signaling involves intracellular phosphorylation cascades including ERK1/2.
机译:子宫颈癌的病因主要取决于人类乳头瘤病毒的感染,但是吸烟是该癌症最重要的行为危险因素。因此,我们先前已证实烟碱乙酰胆碱受体(nAChRs)参与宫颈癌生物学。为了全面评估胆碱能信号在宫颈细胞中的作用,我们研究了毒蕈碱乙酰胆碱受体(mAChRs)的其他参与。我们通过逆转录PCR和Western印迹研究了mAChR和胆碱能系统成分的表达,研究了宫颈的运动性宫颈癌细胞HeLa,SiHa和CaSki表达五个mAChR中的四个,即M1,M3,M4和M5,以及乙酰胆碱(ACh)合成和降解酶胆碱乙酰转移酶(ChAT),乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)和囊泡ACh转运蛋白(VAChT)。 mAChR依赖的信号传导诱导子宫颈细胞运动,需要ERK1 / 2激活,并且可以被mAChR拮抗剂废除。流行病学发现烟草烟雾提高了子宫颈癌的发病率,从而导致了对子宫颈生物学和致癌性胆碱能信号的分析。宫颈癌细胞表达几种nAChR和mAChR,它们的激活会导致细胞特性发生变化,例如运动性和增殖性增加,从而有利于致癌表型。该信号传导涉及包括ERK1 / 2在内的细胞内磷酸化级联反应。

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