PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1/Twist1 pathway

被引：80

作者：

Chen, Jinhuang ^{[1
]}

Yuan, Wenzheng ^{[1
]}

Wu, Liang ^{[1
]}

Tang, Qiang ^{[1
]}

Xia, Qinghua ^{[1
]}

Ji, Jintong ^{[1
]}

Liu, Zhengyi ^{[1
]}

Ma, Zhijun ^{[1
]}

Zhou, Zili ^{[1
]}

Cheng, Yifeng ^{[1
]}

Shu, Xiaogang ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Gastrointestinal Surg, Wuhan, Peoples R China

来源：

ONCOTARGET | 2017年 / 8卷 / 06期

关键词：

PDGF-D; colorectal cancer; EMT; angiogenesis; EPITHELIAL-MESENCHYMAL TRANSITION; FACTOR-RECEPTOR-BETA; EXPRESSION; PROGRESSION; NOTCH-1; OVEREXPRESSION; PHENOTYPE; MODEL; LEADS;

D O I：

10.18632/oncotarget.14283

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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-beta 1) 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.

引用

页码：9961 / 9973

页数：13

共 22 条

[1]

RETRACTED: Platelet-derived growth factor-D contributes to aggressiveness of breast cancer cells by up-regulating Notch and NF-κB signaling pathways (Retracted article. See vol. 158, pg. 605, 2016) [J].