PTPRB promotes metastasis of colorectal carcinoma via inducing epithelial-mesenchymal transition

Xingyue Weng,Yinkuan Shao,Jiani Chen,Shu Zheng,Demin Lu,Xi Zheng,Wangxiong Hu,Kailun Xu,Chenyang Ye,Wei Chen,Lina Qi

doi:10.1038/s41419-019-1554-9

Xingyue Weng, Yinkuan Shao + Show 9 more

Open Access

https://doi.org/10.1038/s41419-019-1554-9

Copy DOI

Abstract

Dysregulation of protein tyrosine phosphatase, receptor type B (PTPRB) correlates with the development of a variety of tumors. Here we show that PTPRB promotes metastasis of colorectal cancer (CRC) cells via inducing epithelial-mesenchymal transition (EMT). We find that PTPRB is expressed at significantly higher levels in CRC tissues compared to adjacent nontumor tissues and in CRC cell lines with high invasion. PTPRB knockdown decreased the number of invasive CRC cells in an in vitro wound healing model, and also reduced tumor metastasis in vivo. Conversely, PTPRB overexpression promoted CRC cell invasion in vitro and metastasis in vivo. PTPRB overexpression decreased vimentin expression and promoted E-cadherin expression, consistent with promotion of EMT, while PTPRB knockdown had the opposite effect. Hypoxic conditions induced EMT and promoted invasion in CRC cells, but these effects were eliminated by PTPRB knockdown. EMT blockade via TWIST1 knockdown inhibited the migration and invasiveness of CRC cells, and even increased PTPRB expression could not reverse this effect. Altogether, these data support the conclusion that PTPRB promotes invasion and metastasis of CRC cells via inducing EMT, and that PTPRB would be a novel therapeutic target for the treatment of CRC.

Highlights

Colorectal cancer (CRC) is one of the most common cancers, and is diagnosed in more than 1 million patients each year[1]
PTPRB is associated with the motility and invasiveness of CRC cells
The expression of PTPRB at both the transcriptional level (Fig. 1c) and protein level (Fig. 1d) was high in LOVO, intermediate in HCT116, and low in HT29 cells. These results indicate that the expression of PTPRB in cells with different motility rates was different

Summary

Introduction

Colorectal cancer (CRC) is one of the most common cancers, and is diagnosed in more than 1 million patients each year[1]. CRC is the fourth most common cause of cancer-related deaths after lung, liver, and stomach cancer[2]. Surgical resection has been considered as the most effective treatment for patients with CRC. Metastasis and recurrence are believed to be responsible for limiting long-term survival of patients with CRC, and there is an estimated recurrence rate of 29–63% among patients with stage II–III CRC4. According to previously reported data, the long-term survival of CRC patients with liver metastasis is rarely longer than three years[5]. Further understanding the vital mechanisms underlying CRC progression is urgent for developing new therapeutic strategies to improve prognosis

Methods

Results

Conclusion