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Cell Death Dis ; 10(5): 352, 2019 04 30.
Article in English | MEDLINE | ID: mdl-31040266

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.


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