PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1/Twist1 pathway.
PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1/Twist1 pathway.
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PDGF-D通过激活Notch1/Twist1通路促进结直肠癌细胞生长、侵袭性、血管生成和EMT转化
DOI：
10.18632/oncotarget.14283
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发表时间：
2017-02-07
期刊：
影响因子：
--
通讯作者：
Shu X
中科院分区：
文献类型：
--
作者：
Chen J;Yuan W;Wu L;Tang Q;Xia Q;Ji J;Liu Z;Ma Z;Zhou Z;Cheng Y;Shu X
血小板衍生生长因子-D (PDGF-D) 在多种癌症的进展中发挥着至关重要的作用。然而，其在结直肠癌（CRC）中的作用仍不清楚。我们的研究表明PDGF-D在结直肠癌组织中高表达，并且与临床病理特征呈正相关。 PDGF-D的下调在体外和体内抑制SW480细胞的肿瘤生长、迁移和血管生成。而PDGF-D的上调促进了HCT116细胞的恶性行为。此外，PDGF-D 上调 CRC 细胞中 Notch1 和 Twist1 的表达。此外，PDGF-D表达促进上皮向间质转化（EMT），同时伴随E-钙粘蛋白减少和波形蛋白表达增加。一致的是，PDGF-D、Notch1 和 Twist1 在转化生长因子-β 1 (TGF-β1) 处理的 HCT116 细胞中明显上调。由于Notch1和Twist1在EMT和肿瘤进展中发挥重要作用，我们检查了Notch1和Twist1在EMT状态中是否存在相关性。我们的结果表明，Notch1 的上调能够挽救 SW480 细胞中 PDGF-D 下调对 Twist1 表达的影响，而 Notch1 下调则降低 HCT116 细胞中 Twist1 的表达。此外，我们发现 Twist1 促进了 CRC 细胞的 EMT 和侵袭性。这些结果表明PDGF-D促进肿瘤生长和CRC的侵袭性，此外，PDGF-D的下调使Notch1/Twist1轴失活，这可以逆转EMT并阻止CRC进展。
Platelet-derived growth factor-D (PDGF-D) plays a crucial role in the progression of several cancers. However, its role in colorectal cancer (CRC) remains unclear. Our study showed that PDGF-D was highly expressed in CRC tissues and was positively associated with the clinicopathological features. Down-regulation of PDGF-D inhibited the tumor growth, migration and angiogenesis of SW480 cells in vitro and in vivo. Whereas up-regulation of PDGF-D promoted the malignant behaviors of HCT116 cells. Moreover, PDGF-D up-regulated the expression of Notch1 and Twist1 in CRC cells. In addition, PDGF-D expression promoted Epithelial to mesenchymal transition (EMT), which was accompanied with decreased E-cadherin and increased Vimentin expression. Consistently, PDGF-D, Notch1, and Twist1 are obviously up-regulated in transforming growth factor-beta 1 (TGF-β1) treated HCT116 cells. Since Notch1 and Twist1 play an important role in EMT and tumor progression, we examined whether there is a correlation between Notch1 and Twist1 in EMT status. Our results showed that up-regulation of Notch1 was able to rescue the effects of PDGF-D down-regulation on Twist1 expression in SW480 cells, whereas down-regulation of Notch1 reduced Twist1 expression in HCT116 cells. Furthermore, we found that Twist1 promoted EMT and aggressiveness of CRC cells. These results suggest that PDGF-D promotes tumor growth and aggressiveness of CRC, moreover, down-regulation of PDGF-D inactivates Notch1/Twist1 axis, which could reverse EMT and prevent CRC progression.