Nicotine Induces Progressive Properties of Lung Adenocarcinoma A549 Cells by Inhibiting Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Expression and Plasma Membrane Localization.
Nicotine Induces Progressive Properties of Lung Adenocarcinoma A549 Cells by Inhibiting Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Expression and Plasma Membrane Localization.
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尼古丁通过抑制囊性纤维化跨膜电导调节因子 (CFTR) 表达和质膜定位诱导肺腺癌 A549 细胞的进展特性
DOI：
10.1177/1533033818809984
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Li H;Ma N;Wang J;Wang Y;Yuan C;Wu J;Luo M;Yang J;Chen J;Shi J;Liu X
肺癌仍然是全球最常见的癌症相关死亡之一。吸烟是肺癌发生的危险因素。有趣的是，CFTR 基因编码的囊性纤维化跨膜电导调节因子是一种 ATP 结合盒转运蛋白类离子通道，可跨上皮细胞膜传导氯离子和碳酸氢根阴离子，最近被认为在多种癌症的发生和进展中发挥作用。有充分证据表明，CFTR 基因突变是导致囊性纤维化的原因，囊性纤维化是白种人群体中最常见的致命性遗传性肺病；然而，囊性纤维化跨膜电导调节剂在肺癌发展中的功能尚未确定。在本研究中，我们旨在通过评估囊性纤维化跨膜电导调节剂对细胞迁移、侵袭和克隆形成的能力以及肺腺癌细胞A549细胞中细胞增殖标记物和肺干细胞相关转录因子的表达，探讨囊性纤维化跨膜电导调节剂对尼古丁促进的肺腺癌细胞进展效力的影响。尼古丁暴露能够增强腺癌细胞（包括 A549 细胞、HCC827 细胞和 PC-9 细胞）的进展特性，并单独抑制囊性纤维化跨膜电导调节蛋白的表达。值得注意的是，囊性纤维化跨膜电导调节因子的过度表达显着抑制了 A549 细胞的进展潜能，包括细胞迁移、侵袭和克隆形成的能力，同时细胞增殖标志物 Ki67、p63 和增殖细胞核抗原、癌症干细胞标志物 CD133、干细胞多能性相关转录因子八聚体结合转录因子 3/4 和性别决定区 Y-box 的表达降低。 2、无论尼古丁的存在与否。相反，在A549细胞中观察到相反的作用，即囊性纤维化跨膜电导调节因子被短发夹RNA敲低。因此，这项研究表明囊性纤维化跨膜电导调节剂可能在肺癌细胞中发挥肿瘤抑制作用，这可能是一个值得进一步研究的新治疗靶点。
Lung cancer remains one of the most common cancer-related deaths worldwide. The cigarette smoking is a risk factor for lung cancer development. Interestingly, the cystic fibrosis transmembrane conductance regulator encoded by CFTR gene, an ATP-binding cassette transporter-class ion channel that conducts chloride and bicarbonate anions across membrane of epithelial cells, has recently been suggested to play a role in the development and progression of many types of cancer. It has been well-documented that mutations of CFTR gene are the cause of cystic fibrosis, the most common fatal hereditary lung disease in Caucasian population; the function of cystic fibrosis transmembrane conductance regulator in the development of lung cancer however has not yet been established. In the present study, we aimed to interrogate the impact of cystic fibrosis transmembrane conductance regulator on the nicotine-promoted progressive potency in lung adenocarcinoma cells by assessing capacities of cystic fibrosis transmembrane conductance regulator to cell migration, invasion, and clonogenicity and the expression of markers of cell proliferation and lung stem cell–related transcription factors in lung adenocarcinoma A549 cells. The exposure of nicotine exhibited an ability to enhance progressive properties of adenocarcinoma cells including A549 cells, HCC827 cells, and PC-9 cells, alone with an inhibition of cystic fibrosis transmembrane conductance regulator protein expression. Remarkably, an overexpression of cystic fibrosis transmembrane conductance regulator significantly inhibited the progressive potency of A549 cells, including capacity of cell migration and invasion and clonogenicity, along with a decreased expression of cell proliferative markers Ki67, p63, and proliferating cell nuclear antigen, and cancer stem cell marker CD133, stem cell pluripotency-related transcription factors octamer-binding transcription factor ¾, and sex-determining region Y-box 2, regardless of the presence of nicotine. In contrast, opposite effects were observed in A549 cells that the cystic fibrosis transmembrane conductance regulator was knockdown by short hairpin RNA to cystic fibrosis transmembrane conductance regulator. This study thus suggests that cystic fibrosis transmembrane conductance regulator may play a tumor suppressor role in lung cancer cells, which may be a novel therapeutic target warranted for further investigation.
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影响因子：
3.9
作者：
Naidu S;Garofalo M
通讯作者：
Garofalo M
MicroRNA 在 EGFR 靶向肺癌治疗中的新作用
影响因子：
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作者：
Han F;He J;Li F;Yang J;Wei J;Cho WC;Liu X
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影响因子：
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DOI：
10.1165/rcmb.2011-0171oc
发表时间：
2012-01-01
影响因子：
6.4
作者：
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通讯作者：
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影响因子：
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作者：
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