Chen Jinhuang, Yuan Wenzheng, Wu Liang, Tang Qiang, Xia Qinghua, Ji Jintong, Liu Zhengyi, Ma Zhijun, Zhou Zili, Cheng Yifeng, Shu Xiaogang
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Oncotarget. 2017 Feb 7;8(6):9961-9973. doi: 10.18632/oncotarget.14283.
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.
血小板衍生生长因子-D（PDGF-D）在多种癌症的进展中起关键作用。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CRC组织中高表达，且与临床病理特征呈正相关。下调PDGF-D可在体外和体内抑制SW480细胞的肿瘤生长、迁移和血管生成。而上调PDGF-D则促进HCT116细胞的恶性行为。此外，PDGF-D上调CRC细胞中Notch1和Twist1的表达。另外，PDGF-D表达促进上皮-间质转化（EMT），伴随E-钙黏蛋白表达降低和波形蛋白表达增加。一致地，在转化生长因子-β1（TGF-β1）处理的HCT116细胞中，PDGF-D、Notch1和Twist1明显上调。由于Notch1和Twist1在EMT和肿瘤进展中起重要作用，我们研究了EMT状态下Notch1和Twist1之间是否存在相关性。我们的结果表明，上调Notch1能够挽救PDGF-D下调对SW480细胞中Twist1表达的影响，而下调Notch1则降低HCT116细胞中Twist1的表达。此外，我们发现Twist1促进CRC细胞的EMT和侵袭性。这些结果表明，PDGF-D促进CRC的肿瘤生长和侵袭性，此外，下调PDGF-D可使Notch1/Twist1轴失活，这可能逆转EMT并阻止CRC进展。
