# Role of the Syx-RhoA signaling axis in glioma cell growth and dissemination

> **NIH NIH R01** · MAYO CLINIC  JACKSONVILLE · 2022 · $342,835

## Abstract

A major issue in the management of brain tumors is their aggressive growth and invasion into surrounding
normal brain tissue. Unfortunately, our understanding of the mechanisms that underlie the aggressive behavior
of these tumors is very limited. Recent evidence indicates that the invasiveness of solid tumors involves
signaling events downstream of Rho GTPases. The Rho family of small GTPases in general and RhoA in
particular, are critical regulators of directed cell migration, cell division, and monolayer patency. Our basic
research findings on the mechanics of cell migration have identified the Rho guanine exchange factor (GEF)
Syx as important in promoting directed cell migration, via its interaction with members of the Crumbs polarity
complex, and activation of RhoA signaling. Interestingly, Syx is highly expressed in human gliomas.
Preliminary studies show that in addition to suppressing cell migration, depletion of Syx drastically impairs
glioma cell division, and significantly improves animal survival in a xenograft mouse model of GBM.
Additionally, inhibition of Syx signaling in cultured glioma cells strongly synergizes with Temozolomide (TMZ),
the standard of care therapy for GBM. The overall scientific premise of this project is that Syx signaling plays a
key role in GBM cell growth, migration and invasion, as well as in responsiveness to chemotherapeutics. As
such, we hypothesize that therapeutic targeting of the Syx-RhoA signaling axis can suppress both the
aggressive growth and invasion of human gliomas and synergize with standard-of-care therapy. To further
characterize the role of Syx in the aggressive growth and invasiveness of human GBM and to test the efficacy
of targeting Syx signaling in combination with standard GBM therapy, we will use cultured cells, organotypic
cultures, animal models of human GBM, as well as human GBM tissue samples, to:
 1. Characterize the effect of Syx depletion on GBM aggressiveness.
 2. Identify key components of the Syx-RhoA signaling axis.
 3. Determine whether inhibition of Syx can enhance the efficacy of chemotherapeutics.

## Key facts

- **NIH application ID:** 10148826
- **Project number:** 5R01NS101721-04
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Panagiotis Z. Anastasiadis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $342,835
- **Award type:** 5
- **Project period:** 2018-05-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148826

## Citation

> US National Institutes of Health, RePORTER application 10148826, Role of the Syx-RhoA signaling axis in glioma cell growth and dissemination (5R01NS101721-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10148826. Licensed CC0.

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