Malignant peripheral nerve sheath tumors (
MPNST) are aggressive
sarcomas with over half of cases developed in the context of
neurofibromatosis type 1. Surgical resection is the only effective
therapy for
MPNST. The prognosis is very dismal once recurrence or
metastasis occurs. Epithelial-mesenchymal transition (EMT) is a key process of recurrence and
metastasis involving reorganizations of the actin cytoskeleton and
actin-binding proteins (ABP) play a non-negligible role.
Protein tyrosine phosphatase receptor S (PTPRS), a
tumor suppressor previously reported in
colorectal cancer,
hepatocellular carcinoma and
head and neck cancer, is thought to mediate cell migration and invasion by downregulation of EMT. However, its role in
MPNST remains unknown. In the present study, by using tissue microarray we demonstrated low expression of PTPRS was related to poor prognosis in
MPNST. Knockdown of PTPRS in
MPNST cell lines increased migration/invasion and EMT processes were induced with increased
N-cadherin and decreased
E-cadherin, which indicated PTPRS may serve as a
tumor suppressor in
MPNST. In addition, we tested all EMT related ABP and found
profilin 1 was significantly elevated in PTPRS downregulated
MPNST cell lines. As a member of
actin-binding proteins,
profilins are regulators of actin polymerization and contribute to cell motility and invasion, which have been reported to be responsible for EMT. Moreover, results showed that downregulation of
profilin 1 could restore the EMT processes caused by PTPRS downregulation in vitro and in vivo. Furthermore, high expression of
profilin 1 was significantly associated with dismal prognosis. These results highlighted PTPRS served as a potential
tumor suppressor in the recurrence and
metastasis of
MPNST via
profilin 1 induced EMT processes and it might provide potential targets for future clinical
therapeutics.