ADAM22 activates integrin β1 through its disintegrin domain to promote the progression of pituitary adenoma.

ADAM22 PKA integrin β1 invasion pituitary adenoma

Journal

Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420

Informations de publication

Date de publication:
09 Aug 2023
Historique:
received: 03 03 2023
medline: 9 8 2023
pubmed: 9 8 2023
entrez: 9 8 2023
Statut: aheadofprint

Résumé

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.

Sections du résumé

BACKGROUND BACKGROUND
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.
METHODS METHODS
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.
RESULTS RESULTS
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.
CONCLUSIONS CONCLUSIONS
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.

Identifiants

DOI: 10.1093/neuonc/noad148 PMID: 37555799
pubmed: 37555799
pii: 7239911
doi: 10.1093/neuonc/noad148
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 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.

Auteurs

Biao Xing (B)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Zhuowei Lei (Z)

Department of Orthopedics, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Zihan Wang (Z)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Quanji Wang (Q)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Qian Jiang (Q)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Zhuo Zhang (Z)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Xiaojin Liu (X)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Yiwei Qi (Y)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Sihan Li (S)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Xiang Guo (X)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Yanchao Liu (Y)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Xingbo Li (X)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Kai Shu (K)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Huaqiu Zhang (H)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Jörg-Walter Bartsch (JW)

Department of Neurosurgery, Philipps-University Marburg, University Hospital Marburg (UKGM), Baldingerstrasse, 35043 Marburg, Germany.
Marburg Center for Mind, Brain and Behavior (MCMBB), 35032 Marburg, Germany.

Christopher Nimsky (C)

Department of Neurosurgery, Philipps-University Marburg, University Hospital Marburg (UKGM), Baldingerstrasse, 35043 Marburg, Germany.
Marburg Center for Mind, Brain and Behavior (MCMBB), 35032 Marburg, Germany.

Yimin Huang (Y)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Ting Lei (T)

Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, 430030, China.

Classifications MeSH