# Wnt/Planar Cell Polarity Contribution to Glioblastoma Multiforme Invasion and Therapeutic Resistance

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $38,195

## Abstract

Project Summary
Glioblastoma multiforme (GBM) is the most common form of malignant brain cancer, and is highly aggressive,
recurrent, and difficult to treat. The highly infiltrative nature of GBM cells diminishes the clinical efficacy of
surgery, and while the prospect of more effective patient-tailored therapies has been explored, such strategies
have thus far failed because tumors are invariably highly resistant. Wnt/Planar Cell Polarity (PCP) is a non-
canonical Wnt signaling pathway that promotes global directional cues to produce locally polarized cell behavior,
leading to increased cell motility, survival and proliferation. Wnt/PCP is critical for embryonic developmental
processes, where it modulates cell adhesion and migration. The emerging role for Wnt/PCP signaling in tumor
malignancy solidifies the recurring theme that tumors reactivate developmental programs to promote their
aggressive behaviors. Expression patterns of Wnt/PCP pathway components strongly suggest that GBM tumors
engage the pathway to promote invasiveness and therapeutic resistance, underscoring the notion that a deeper
understanding of Wnt/PCP in GBM could uncover novel therapeutic approaches. The hypothesis driving the
proposed studies is that Wnt/PCP signaling directly contributes to the malignant properties of GBM, including
proliferation, motility, invasiveness and therapeutic resistance. Specific Aim 1 will rigorously characterize the
mechanisms by which Wnt/PCP signaling drives the malignant properties of GBM using cellular, molecular and
biochemical techniques, focusing on the involvement of the Wnt5a/Fzd7 ligand/receptor pair. Specific Aim 2 will
employ knockdown and exogenous expression methods to determine the extent to which PCP components
contribute to GBM resistance to targeted therapeutics. Recapitulation of in vitro findings in vivo will be examined
in Specific Aim 3 using orthotopic and patient-derived xenograft mouse models of GBM. The successful
completion of the project will solidify the involvement of the Wnt/PCP pathway in GBM malignancy, and reveal
novel targets for therapeutic intervention into the disease.

## Key facts

- **NIH application ID:** 10071868
- **Project number:** 5F31CA246900-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Courtney Anne Dreyer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,195
- **Award type:** 5
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071868

## Citation

> US National Institutes of Health, RePORTER application 10071868, Wnt/Planar Cell Polarity Contribution to Glioblastoma Multiforme Invasion and Therapeutic Resistance (5F31CA246900-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071868. Licensed CC0.

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