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

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.

• Authors: Xingyue Weng, Wei Chen, Wangxiong Hu, Kailun Xu, Lina Qi, Jiani Chen, Demin Lu, Yinkuan Shao, Xi Zheng, Chenyang Ye, Shu Zheng
• Journal: Cell death & disease (Cell Death Dis) Vol. 10 Issue 5 Pg. 352 (04 30 2019) ISSN: 2041-4889 [Electronic] England
• PMID: 31040266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• Nuclear Proteins
• RNA, Small Interfering
• TWIST1 protein, human
• Twist-Related Protein 1
• PTPRB protein, human
• Receptor-Like Protein Tyrosine Phosphatases, Class 3

Topics

• Animals
• Cadherins (metabolism)
• Cell Line, Tumor
• Cell Movement
• Colorectal Neoplasms (drug therapy, metabolism, pathology)
• Epithelial-Mesenchymal Transition
• Humans
• Male
• Mice
• Mice, Nude
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Nuclear Proteins (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism, therapeutic use)
• Receptor-Like Protein Tyrosine Phosphatases, Class 3 (antagonists & inhibitors, genetics, metabolism)
• Transplantation, Heterologous
• Twist-Related Protein 1 (antagonists & inhibitors, genetics, metabolism)