Hypoxia induces tumor cell growth and angiogenesis in non-small cell lung carcinoma via the Akt-PDK1-HIF1α-YKL-40 pathway.
Hypoxia induces tumor cell growth and angiogenesis in non-small cell lung carcinoma via the Akt-PDK1-HIF1α-YKL-40 pathway.
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缺氧通过 Akt-PDK1-HIF1α-YKL-40 途径诱导非小细胞肺癌肿瘤细胞生长和血管生成
DOI：
10.21037/tcr.2020.03.80
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发表时间：
2020-04
影响因子：
0.9
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Miao Y;Wang W;Dong Y;Hu J;Wei K;Yang S;Lai X;Tang H
非小细胞肺癌（NSCLC）是最常见的癌症之一，以缺氧为特征。转录因子缺氧诱导因子（hypoxia inducible factor， HIF）-1α是响应缺氧并调控多种相关因子的主要介质。缺氧调节的各种模式经常成为研究的焦点。参考前人发表的研究，我们假设缺氧通过Akt-PDK1-HIF1α-YKL-40通路促进NSCLC的生长和血管生成，并进行了验证。我们主要研究不同处理的CL1-5细胞中相关因子的表达变化。采用过表达、过表达转染、Western blot、rt-PCR、ELISA等方法，通过CCK-8迁移侵袭实验、成管实验观察细胞生物学行为。缺氧环境显著增加线粒体中Akt和PDK1的磷酸化。缺氧诱导的线粒体中p-Akt的积累激活了PDK1的磷酸化，促进了HIF1α的表达和YKL-40的表达。YKL-40的过表达促进了CL1-5细胞的增殖、迁移、侵袭和小管形成。低氧肿瘤微环境可通过Akt-PDK1-HIF1α-YKL-40通路促进NSCLC细胞的增殖和血管生成。这可能为抗血管性肺癌的治疗提供新的机制和潜在的介入靶点。
As one of the most common forms of cancer, non-small cell lung carcinoma (NSCLC), is characterized by oxygen deprivation (hypoxia). The transcription factor hypoxia-inducible factor (HIF)-1α is a major mediator which responds hypoxia and regulates many contributing factors. The various modes of hypoxia regulation are frequently the focus of research studies. With reference to previous published research, we hypothesized that hypoxia promotes the growth and angiogenesis of NSCLC via the Akt-PDK1-HIF1α-YKL-40 pathway, and verified it. We mainly investigated changes in related factor expression between differently treated CL1-5 cells. We carried out overexpression and underexpression transfection, Western blot, rt-PCR and ELISA, and observed cellular biological behaviors by CCK-8 migration and invasion assay, and tube formation assay. A hypoxic environment significantly increased the phosphorylation of Akt and PDK1 in mitochondria. The hypoxia-induced accumulation of p-Akt in mitochondria activated PDK1 phosphorylation, promoted the expression of HIF1α, and the expression of YKL-40. The overexpression of YKL-40 promoted the proliferation, migration, invasion and tubule formation of CL1-5 cells. A hypoxic tumor microenvironment can promote the expansion and angiogenesis of NSCLC cells through the Akt-PDK1-HIF1α-YKL-40 pathway. This may provide a new mechanism and potential interventional target for anti-vascular lung cancer therapy.
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影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
8
作者：
Kawada, M.;Seno, H.;Kanda, K.;Nakanishi, Y.;Akitake, R.;Komekado, H.;Kawada, K.;Sakai, Y.;Mizoguchi, E.;Chiba, T.
通讯作者：
Chiba, T.
影响因子：
50.3
作者：
Chae YC;Vaira V;Caino MC;Tang HY;Seo JH;Kossenkov AV;Ottobrini L;Martelli C;Lucignani G;Bertolini I;Locatelli M;Bryant KG;Ghosh JC;Lisanti S;Ku B;Bosari S;Languino LR;Speicher DW;Altieri DC
通讯作者：
Altieri DC
影响因子：
4.7
作者：
Bijur, GN;Jope, RS
通讯作者：
Jope, RS
影响因子：
4.8
作者：
Lu, HS;Dalgard, CL;Verma, A
通讯作者：
Verma, A