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MFAP2 Promotes Glioblastoma Malignant Phenotypes via Autophagy-Dependent Activation of Wnt/β-Catenin Signaling
Peihao Yang1, Demeng Liu1, Jiyao Wang2
1Department of Pharmacy, The Second Affiliated Hospital of Zhengzhou University, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450053, China.
Abstract:
Background: Microfibrillar-associated protein 2 (MFAP2) is implicated in various malignancies, yet its specific role and molecular mechanisms in glioblastoma (GBM) progression remain poorly understood. Methods: We analyzed MFAP2 expression in human clinical specimens and murine models. Functional impacts were assessed in U251 cells via gain- and loss-of-function assays. Mechanistic studies explored the interplay between autophagic flux and Wnt/β-catenin signaling. An orthotopic GL261 syngeneic orthotopic model validated these findings in vivo. Results: MFAP2 was significantly overexpressed in GBM, correlating with poor patient prognosis. In vitro, MFAP2 markedly enhanced U251 viability, migration, and invasion while suppressing apoptosis. Mechanistically, MFAP2 triggered autophagic flux, subsequently activating the Wnt/β-catenin cascade and its downstream targets (MMP9, c-Myc, Cyclin D1). Pharmacological inhibition of either autophagy or Wnt signaling effectively abrogated these oncogenic phenotypes. In vivo, MFAP2 knockdown reduced tumor volume by 62.4% and suppressed the autophagy-Wnt axis. Conclusions: MFAP2 is an oncogenic regulator in glioblastoma models that links autophagy activity to Wnt/β-catenin signaling. Our findings support MFAP2 as a candidate prognostic biomarker and a potential therapeutic target; however, additional validation in larger molecularly annotated clinical cohorts and multiple GBM models is warranted.
Insights
Microfibrillar-associated protein 2 (MFAP2) drives glioblastoma growth by activating autophagy and Wnt/β-catenin signaling. MFAP2 is a potential prognostic biomarker and therapeutic target for glioblastoma (GBM).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling
Background:
- Microfibrillar-associated protein 2 (MFAP2) is linked to cancers, but its role in glioblastoma (GBM) is unclear.
- Understanding MFAP2's function is crucial for developing new GBM therapies.
Purpose of the Study:
- To investigate the role and molecular mechanisms of MFAP2 in glioblastoma progression.
- To evaluate MFAP2 as a potential prognostic biomarker and therapeutic target in GBM.
Main Methods:
- Analyzed MFAP2 expression in clinical GBM samples and animal models.
- Conducted in vitro gain/loss-of-function assays and in vivo orthotopic xenograft models.
- Explored the interplay between autophagic flux and Wnt/β-catenin signaling pathways.
Main Results:
- MFAP2 was overexpressed in GBM and correlated with poor prognosis.
- MFAP2 enhanced GBM cell viability, migration, and invasion by activating autophagy and the Wnt/β-catenin pathway.
- MFAP2 knockdown reduced tumor growth and suppressed the autophagy-Wnt axis in vivo.
Conclusions:
- MFAP2 acts as an oncogenic driver in GBM, linking autophagy to Wnt/β-catenin signaling.
- MFAP2 shows promise as a prognostic biomarker and therapeutic target for GBM.
- Further validation in larger clinical cohorts and diverse GBM models is recommended.
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