丛状神经纤维瘤 (PNF) 是一种与 NF1 相关的常见且严重的表型，其特点是致畸率高和恶变的可能性。 PNF 的生长和复发归因于 Nf1 缺陷雪旺细胞的异常增殖和迁移。蛋白酪氨酸磷酸酶受体 S (PTPRS) 被认为通过抑制 NF1 衍生的恶性周围神经鞘瘤的 EMT 过程来调节细胞迁移和侵袭。然而，PTPRS 在 NF1 衍生的 PNF 中的具体作用仍有待阐明。该研究利用 GEO 数据库和组织微阵列来说明 PNF 组织中 PTPRS 表达的减少，这与肿瘤复发有关。此外，Nf1缺陷的雪旺细胞系中PTPRS的下调和过表达导致细胞迁移和EMT过程的变化。此外，RTK 测定和 WB 显示 PTPRS 敲低可以促进 EGFR 表达和磷酸化。雪旺细胞中因 PTPRS 水平改变而中断的 EMT 过程的恢复可以通过 EGFR 敲低和 EGFR 抑制剂来实现。此外，EGFR 高表达与不良预后显着相关。这些发现强调了 PTPRS 通过调节 EGFR 介导的 EMT 过程作为肿瘤抑制因子在 PNF 复发中的潜在作用，提出了未来临床干预的潜在目标。版权所有 © 2024。由 Elsevier B.V. 出版。

Plexiform neurofibromas (PNFs) are a prevalent and severe phenotype associated with NF1, characterized by a high teratogenic rate and potential for malignant transformation. The growth and recurrence of PNFs are attributed to aberrant proliferation and migration of Nf1-deficient Schwann cells. Protein tyrosine phosphatase receptor S (PTPRS) is believed to modulate cell migration and invasion by inhibiting the EMT process in NF1-derived malignant peripheral nerve sheath tumors. Nevertheless, the specific role of PTPRS in NF1-derived PNFs remains to be elucidated. The study utilized the GEO database and tissue microarray to illustrate a decrease in PTPRS expression in PNF tissues, linked to tumor recurrence. Furthermore, the down- and over-expression of PTPRS in Nf1-deficient Schwann cell lines resulted in the changes of cell migration and EMT processes. Additionally, RTK assay and WB showed that PTPRS knockdown can promote EGFR expression and phosphorylation. The restoration of EMT processes disrupted by alterations in PTPRS levels in Schwann cells can be achieved through EGFR knockdown and EGFR inhibitor. Moreover, high EGFR expression has been significantly correlated with poor prognosis. These findings underscore the potential role of PTPRS as a tumor suppressor in the recurrence of PNF via the regulation of EGFR-mediated EMT processes, suggesting potential targets for future clinical interventions.Copyright © 2024. Published by Elsevier B.V.