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Tumor cell-derived angiopoietin-like protein 2 establishes a preference for glycolytic metabolism in lung cancer cells.

肿瘤细胞来源的血管生成素样蛋白 2 在肺癌细胞中建立了对糖酵解代谢的偏好。

  • 影响因子:0
  • DOI:10.1111/cas.14337
  • 作者列表:"Osumi H","Horiguchi H","Kadomatsu T","Tashiro K","Morinaga J","Takahashi T","Ikeda K","Ito T","Suzuki M","Endo M","Oike Y
  • 发表时间:2020-04-01
Abstract

:We previously revealed that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates the metastatic capacity of tumors in an autocrine/paracrine manner by activating tumor cell motility and invasiveness and the epithelial-mesenchymal transition. However, the effects of ANGPTL2 on cancer cell glycolytic metabolism, which is a hallmark of tumor cells, are unknown. Here we report evidence supporting a role for tumor cell-derived ANGPTL2 in establishing a preference for glycolytic metabolism. We report that a highly metastatic lung cancer cell subline expressing abundant ANGPTL2 showed upregulated expression of the glucose transporter GLUT3 as well as enhanced glycolytic metabolism relative to a less metastatic parental line. Most notably, ANGPTL2 overexpression in the less metastatic line activated glycolytic metabolism by increasing GLUT3 expression. Moreover, ANGPTL2 signaling through integrin α5β1 increased GLUT3 expression by increasing transforming growth factor-β (TGF-β) signaling and expression of the downstream transcription factor zinc finger E-box binding homeobox 1 (ZEB1). Conversely, ANGPTL2 knockdown in the highly metastatic subline decreased TGF-β1, ZEB1, and GLUT3 expression and antagonized glycolytic metabolism. In primary tumor cells from patients with lung cancer, ANGPTL2 expression levels correlated with GLUT3 expression. Overall, this work suggests that tumor cell-derived ANGPTL2 accelerates activities associated with glycolytic metabolism in lung cancer cells by activating TGF-β-ZEB1-GLUT3 signaling.

摘要

: 我们之前发现肿瘤细胞来源的血管生成素样蛋白 2 (ANGPTL2) 通过激活肿瘤细胞运动性和侵袭性以及上皮-间质转化,以自分泌/旁分泌方式加速肿瘤的转移能力。然而,ANGPTL2 对作为肿瘤细胞标志的癌细胞糖酵解代谢的作用是未知的。在这里,我们报道了支持肿瘤细胞来源的ANGPTL2 在建立糖酵解代谢偏好中的作用的证据。我们报告了一个表达丰富ANGPTL2 的高转移性肺癌细胞亚系,相对于转移较少的亲代细胞系,显示葡萄糖转运蛋白GLUT3 的表达上调以及糖酵解代谢增强。最值得注意的是,在转移较少的细胞系中,ANGPTL2 过表达通过增加GLUT3 表达而激活糖酵解代谢。此外,通过整合素 α5β1 的ANGPTL2 信号通过增加转化生长因子-β (TGF-β) 增加GLUT3 的表达下游转录因子锌指E盒结合同源盒 1 (ZEB1) 的信号传导和表达。相反,高转移亚系中的ANGPTL2 敲除降低了TGF-β1 、ZEB1 和GLUT3 表达,并拮抗了糖酵解代谢。在来自肺癌患者的原代肿瘤细胞中,ANGPTL2 表达水平与GLUT3 表达相关。总的来说,这项工作表明肿瘤细胞来源的ANGPTL2 通过激活TGF-β-ZEB1-GLUT3 信号传导来加速肺癌细胞中与糖酵解代谢相关的活动。

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影响因子:6.93
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DOI:10.1002/ijc.32530
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肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

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