Abstract
Malignant peripheral nerve sheath tumours (MPNSTs) are highly aggressive Schwann cell-derived sarcomas, and they are either associated with neurofibromatosis type 1 (NF1) or sporadic. Our previous study found that high mobility group protein A2 (HMGA2) regulates NF1-MPNST growth through Musashi-2 (MSI2); however, whether MSI2 regulates MPNST metastasis and what the mechanism is remain unclear. Here, we demonstrated that the protein caveolin-1 (CAV1) directly interacts with MSI2 in human NF1-MPNST cells. Moreover, we discovered that knockdown of MSI2 induces CAV1 protein expression by inhibiting its ubiquitylation level in NF1-MPNSTs. In addition, CAV1 mediates the suppressive function of MSI2 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to reveal the potential mechanisms of MSI2 as a target of antimetastatic treatment for human NF1-MPNST.
Highlights
Malignant peripheral nerve sheath tumours (MPNSTs) are highly aggressive Schwann cell-derived sarcomas that are either associated with neurofibromatosis type 1 (NF1) or sporadic[1]
Our previous study found that MSI2 knockdown inhibits cell proliferation in NF1-MPNSTs11, so we wanted to determine whether MSI2 could regulate NF1-MPNST cell migration and invasion
We first determined whether MSI2 expression was significantly higher in NF1MPNSTs than it was in neurofibromas through analysis of two MPNST patient cohorts, Jessen_cohort (GEO: GSE41747) and Kolberg_cohort (GEO: GSE66743)
Summary
Malignant peripheral nerve sheath tumours (MPNSTs) are highly aggressive Schwann cell-derived sarcomas that are either associated with NF1 or sporadic[1]. NF1MPNSTs are malignant tumours that are transformed from neurofibromas[2]. The patient’s prognosis is very poor, with death often resulting from lung metastasis[3]. The Musashi family includes Musashi-1 (MSI1) and Musashi-2 (MSI2). Both have about 75% amino acid identity in the overall structure and belong to the RNA binding protein family[4]. MSI1 and MSI2 are highly expressed in various tumours such as glioma, breast cancer, pancreatic cancer, colon cancer, lung cancer, ovarian cancer and prostate cancer[5,6,7,8,9,10]. Whether MSI2 or MSI1, their expression levels in tumours are higher than
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
