Dataset Information

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex.

ABSTRACT:

Background

Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.

Methods

We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility.

Results

ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-β and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs.

Conclusions

Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.

SUBMITTER: Jandrey EHF

PROVIDER: S-EPMC10681280 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating <b>γ</b>-secretase complex.

Jandrey Elisa Helena Farias EHF Barnabé Gabriela Filoso GF Maldaun Marcos M Asprino Paula Fontes PF Dos Santos Natália Cristina NC Inoue Lilian Tiemi LT Rozanski Andrei A Galante Pedro Alexandre Favoretto PAF Marie Suely Kazue Nagahashi SKN Oba-Shinjo Sueli Mieko SM Dos Santos Tiago Góss TG Chammas Roger R Lancellotti Carmen Lucia Penteado CLP Furnari Frank B FB Camargo Anamaria Aranha AA Costa Érico Tosoni ÉT

Neuro-oncology advances 20230101 1

<h4>Background</h4>Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.<h4>Methods</h4>We integrated <i>in vitro</i> and <i>in vivo</i> functional assays, RNA ...[more]

PMID: 38024245

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