Department of Orthopedics, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang middle Rd, 225000, Yangzhou, People's Republic of China.
Department of Urology, Sir Run Run Shaw Hospital, No. 3, Qingchun east Rd, 310000, Hangzhou, People's Republic of China.
Cell Death Dis. 2020 Jun 30;11(6):489. doi: 10.1038/s41419-020-2703-x.
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.
恶性外周神经鞘瘤（MPNST）是一种高度侵袭性的雪旺细胞源性肉瘤，与神经纤维瘤病 1 型（NF1）或散发性相关。我们之前的研究发现，高迁移率族蛋白 A2（HMGA2）通过 Musashi-2（MSI2）调节 NF1-MPNST 的生长；然而，MSI2 是否调节 MPNST 的转移以及其机制尚不清楚。在这里，我们证明了 Cav-1（CAV1）蛋白在人 NF1-MPNST 细胞中直接与 MSI2 相互作用。此外，我们发现，在 NF1-MPNST 中，敲低 MSI2 通过抑制其泛素化水平诱导 CAV1 蛋白表达。此外，CAV1 介导了 MSI2 在体外上皮-间充质转化、迁移和侵袭以及体内转移中的抑制作用。这些结果有助于揭示 MSI2 作为人类 NF1-MPNST 抗转移治疗靶点的潜在机制。
