# Identification of novel regulators of invadopodia formation

> **NIH NIH R03** · UNIVERSITY OF TOLEDO · 2020 · $75,000

## Abstract

ABSTRACT
 The migration of cancer cells away from the primary tumor and their subsequent metastasis to
distant organs is the leading cause of mortality in cancer patients. Metastatic cells escape the primary
tumor and enter the bloodstream by developing specialized cellular structures called invadopodia that
degrade the extracellular matrix (ECM) surrounding the tumor to allow invasion. The assembly of
invadopodia is regulated by a family of proteins called Rho GTPases, which play key roles in virtually all
stages of cancer progression. In contrast to other cancer associated genes that are frequently mutated
in cancer, mutations in Rho genes have been only rarely detected in tumors. In contrast, RhoGEFs and
RhoGAPs, two protein families that function upstream of the Rho GTPases to regulate activity, are often
misregulated or mutated in cancer. Based on these findings, the development of inhibitors targeting
RhoGEFs and RhoGAPs is emerging as a promising approach to cancer therapy, and studies suggest
that such inhibitors appear to block many functions associated with tumorigenesis. The objective of this
study is to identify novel regulators of invadopodia formation within the RhoGEF and RhoGAP families.
This proposal comprises two specific aims: In Aim 1 we will identify the RhoGEF that activates Rac1, an
essential player in invadopodia formation, and in Aim 2, we will screen for RhoGAPs that modulate the
formation of invadopodia. For both aims, we plan to characterize the function of the candidates identified
during invadopodia formation, cell migration and invasion. It is our expectation that the identified
RhoGEFs and RhoGAPs can be used to develop specific inhibitors to slow down or prevent invadopodia
formation and thus, invasion and metastasis in different cancer types.

## Key facts

- **NIH application ID:** 9851349
- **Project number:** 5R03CA234693-02
- **Recipient organization:** UNIVERSITY OF TOLEDO
- **Principal Investigator:** Rafael Garcia-Mata
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $75,000
- **Award type:** 5
- **Project period:** 2019-01-17 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851349

## Citation

> US National Institutes of Health, RePORTER application 9851349, Identification of novel regulators of invadopodia formation (5R03CA234693-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9851349. Licensed CC0.

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