大约35%的垂体腺瘤（PA）表现出侵袭性特点，导致低手术完全切除率、高复发率和恶化预后。然而，PA侵袭的分子机制仍然知之甚少。尽管“A去粘附和金属蛋白酶”（ADAMs）与许多肿瘤的进展有关，但尚无关于PA中ADAM22的报道。利用PA转录组数据库和临床标本分析ADAM22的表达。构建过表达野生型ADAM22、点突变ADAM22、无去粘附结构域的突变ADAM22和敲低ADAM22的PA细胞系。进行细胞增殖/侵袭实验、流式细胞术、免疫组织化学、免疫荧光、共免疫沉淀、质谱分析、RT-qPCR、磷酸标记SDS-PAGE和Western blot等功能和机制研究。利用裸鼠异种移植模型和大鼠催乳素瘤原位模型验证体外结果。ADAM22在PA中明显过表达，可促进PA细胞的增殖、迁移和侵袭。ADAM22通过其去粘附结构域与整合素β1（ITGB1）相互作用，并激活FAK/PI3K和FAK/ERK信号通路，从而促进PA的进展。ADAM22可被PKA磷酸化并招募14-3-3蛋白，从而延迟其降解。ITGB1靶向抑制剂（抗itgb1）对PA具有抗肿瘤效应，并与生长抑素类似物或多巴胺激动剂联合治疗PA时具有协同效应。ADAM22在PA中上调表达，通过激活ITGB1信号通路促进PA的增殖、迁移和侵袭。PKA可以通过转录后修饰水平调控ADAM22的降解。ITGB1可能是PA的潜在治疗靶点。 © 作者（们）2023。由牛津大学出版社代表神经肿瘤学学会发表。保留所有权利。如需授权，请发送电子邮件至：journals.permissions@oup.com。

Approximately 35% of pituitary adenoma (PA) display an aggressive profile, resulting in low surgical total resection rates, high recurrence rates, and worse prognosis. However, the molecular mechanism of PA invasion remains poorly understood. Although 'a disintegrin and metalloproteases' (ADAMs) are associated with the progression of many tumors, there are no reports on ADAM22 in PA.PA transcriptomics databases and clinical specimens were used to analyze the expression of ADAM22. PA cell lines overexpressing wild-type ADAM22, the point mutation ADAM22, the mutated ADAM22 without disintegrin domain, and knocking down ADAM22 were generated. Cell proliferation/invasion assays, flow cytometry, immunohistochemistry, immunofluorescence, co-immunoprecipitation, mass spectrometry, RT-qPCR, phos-tag SDS-PAGE, and Western blot were performed for function and mechanism research. Nude mice xenograft models and rat prolactinoma orthotopic models were used to validate in vitro findings.ADAM22 was significantly overexpressed in PA and could promote the proliferation, migration, and invasion of PA cells. ADAM22 interacted with integrin β1 (ITGB1) and activated FAK/PI3K and FAK/ERK signaling pathways through its disintegrin domain to promote PA progression. ADAM22 was phosphorylated by PKA and recruited 14-3-3, thereby delaying its degradation. ITGB1-targeted inhibitor (anti-itgb1) exerted antitumor effects and synergistic effects in combination with somatostatin analogs or dopamine agonists in treating PA.ADAM22 was upregulated in PA and was able to promote PA proliferation, migration, and invasion by activating ITGB1 signaling. PKA may regulate the degradation of ADAM22 through post-transcriptional modification levels. ITGB1 may be a potential therapeutic target for PA.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.