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.

恶性周围神经鞘瘤（MPNST）是高度侵袭性的Schwann细胞衍生的肉瘤，与1型神经纤维瘤病（NF1）相关或偶发。我们先前的研究发现，高迁移率族蛋白A2（HMGA2）通过Musashi-2（MSI2）调节NF1-MPNST的生长。但是，MSI2是否调节MPNST转移以及其机制尚不清楚。在这里，我们证明了蛋白质caveolin-1（CAV1）与人NF1-MPNST细胞中的MSI2直接相互作用。此外，我们发现敲低MSI2通过抑制其在NF1-MPNSTs中的泛素化水平来诱导CAV1蛋白表达。此外，CAV1介导MSI2在体外上皮-间质转化，迁移和侵袭以及体内转移中的抑制功能。