PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1/Twist1 pathway
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Jinhuang Chen1,*, Wenzheng Yuan1,*, Liang Wu1, Qiang Tang1, Qinghua Xia1, Jintong Ji1, Zhengyi Liu1, Zhijun Ma1, Zili Zhou1, Yifeng Cheng1, Xiaogang Shu1
1Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
*These authors have contributed equally to this work
Xiaogang Shu, email: [email protected]
Keywords: PDGF-D, colorectal cancer, EMT, angiogenesis
Received: August 11, 2016 Accepted: November 30, 2016 Published: December 27, 2016
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.
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