Intracrine VEGF signalling mediates colorectal cancer cell migration and invasion.
Intracrine VEGF signalling mediates colorectal cancer cell migration and invasion.
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DOI：
10.1038/bjc.2017.238
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发表时间：
2017-09-05
影响因子：
8.8
通讯作者：
Ellis LM
中科院分区：
文献类型：
--
作者：
Bhattacharya R;Fan F;Wang R;Ye X;Xia L;Boulbes D;Ellis LM
血管内皮生长因子 (VEGF) 及其受体 (VEGFR) 是血管生成的关键调节因子，影响内皮细胞的存活和功能。然而，VEGF-VEGFR 信号传导对肿瘤细胞功能的影响尚不清楚。我们之前对结直肠癌 (CRC) 细胞的研究表明，内分泌 VEGF/VEGFR1 信号传导机制可介导 CRC 细胞存活和化疗敏感性。由于细胞外 VEGF 信号传导调节内皮细胞和各种肿瘤细胞的迁移，我们试图确定分泌内 VEGF 信号传导是否影响 CRC 细胞运动。使用 Transwell 迁移室测定 CRC 细胞的迁移和侵袭，无论是否有 VEGF 或 VEGFR1 耗尽。通过免疫染色和蛋白质印迹评估细胞形态、上皮间质转化（EMT）标记和细胞运动标记的变化。多种 CRC 细胞系中细胞内 VEGF 和 VEGFR1 的消耗导致 CRC 细胞迁移和侵袭的强烈抑制。除 Twist 外，对照细胞和 VEGF/VEGFR1 缺失的 CRC 细胞之间的 EMT 标志物没有显着差异。然而，VEGF/VEGFR1 耗尽的 CRC 细胞表现出磷酸化粘着斑激酶及其上游调节因子 pcMET 和 pEGFR 水平显着降低。抑制分泌内 VEGF 信号传导可通过调节参与细胞运动的蛋白质来强烈抑制 CRC 细胞迁移和侵袭。
Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) are key regulators of angiogenesis, affecting endothelial cell survival and function. However, the effect of VEGF-VEGFR signalling on tumour cell function is not well understood. Our previous studies in colorectal cancer (CRC) cells have demonstrated an intracrine VEGF/VEGFR1 signalling mechanism that mediates CRC cell survival and chemo-sensitivity. Since extracellular VEGF signalling regulates migration of endothelial cells and various tumour cells, we attempted to determine whether intracrine VEGF signalling affects CRC cell motility. Migration and invasion of CRC cells, with and without VEGF or VEGFR1 depletion, were assayed using transwell migration chambers. Changes in cell morphology, epithelial-mesenchymal transition (EMT) markers, and markers of cell motility were assessed by immunostaining and western blot. Depletion of intracellular VEGF and VEGFR1 in multiple CRC cell lines led to strong inhibition of migration and invasion of CRC cells. Except for Twist, there were no significant differences in markers of EMT between control and VEGF/VEGFR1-depleted CRC cells. However, VEGF/VEGFR1-depleted CRC cells demonstrated a significant reduction in levels of phosphorylated focal adhesion kinase and its upstream regulators pcMET and pEGFR. Inhibition of intracrine VEGF signalling strongly inhibits CRC cell migration and invasion by regulating proteins involved in cell motility.
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影响因子：
82.9
作者：
Du Y;Yamaguchi H;Wei Y;Hsu JL;Wang HL;Hsu YH;Lin WC;Yu WH;Leonard PG;Lee GR 4th;Chen MK;Nakai K;Hsu MC;Chen CT;Sun Y;Wu Y;Chang WC;Huang WC;Liu CL;Chang YC;Chen CH;Park M;Jones P;Hortobagyi GN;Hung MC
通讯作者：
Hung MC
影响因子：
3.3
作者：
Deramaudt TB;Dujardin D;Hamadi A;Noulet F;Kolli K;De Mey J;Takeda K;Rondé P
通讯作者：
Rondé P
影响因子：
15.8
作者：
Lee TH;Seng S;Sekine M;Hinton C;Fu Y;Avraham HK;Avraham S
通讯作者：
Avraham S
影响因子：
4
作者：
Costa, Raquel;Carneiro, Angela;Soares, Raquel
通讯作者：
Soares, Raquel
影响因子：
11.2
作者：
Bhattacharya R;Ye XC;Wang R;Ling X;McManus M;Fan F;Boulbes D;Ellis LM
通讯作者：
Ellis LM