# EPHA2 Receptor Signaling in Breast Cancer Mechanotransduction

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2023 · $520,482

## Abstract

SUMMARY
Mechanical forces generated by a rigid extracellular matrix (ECM) in the tumor microenvironment play a key
role in tumor progression and metastasis. We recently discovered a critical role of EPHA2 non-canonical
signaling in promoting epithelial-mesenchymal transition (EMT) and tumor invasion and metastasis in response
to increasing ECM stiffness in the tumor microenvironment. Furthermore, we found that activation of EPHA2
canonical signaling by the ephrinA1 ligand potently inhibits stiffness-induced breast cancer cell invasiveness.
Based on these results, we hypothesize that EPHA2 functions as a key rheostat that integrates both
mechanical and biochemical cues from the tumor microenvironment to regulate mechanosignaling in breast
cancer progression and metastasis. We propose to combine biochemical, 2D and 3D cell culture assays, and
in vivo xenograft models to elucidate EPHA2 signaling mechanisms in breast cancer malignancy induced by
ECM rigidity through three specific aims. (1) Determine how ECM rigidity activates EPHA2 non-canonical
signaling to promote EMT and invasion. (2) Determine how EPHA2 canonical signaling blocks EMT and
invasion induced by ECM rigidity. (3) Examine the role of EPHA2 non-canonical and canonical signaling in
breast cancer invasion and metastasis in vivo. Together, these studies will inform on the potential usefulness
of activating EphA2 canonical signaling for inhibition of breast cancer invasiveness and metastasis.

## Key facts

- **NIH application ID:** 10609917
- **Project number:** 5R01CA262794-02
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** ELENA B PASQUALE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $520,482
- **Award type:** 5
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10609917

## Citation

> US National Institutes of Health, RePORTER application 10609917, EPHA2 Receptor Signaling in Breast Cancer Mechanotransduction (5R01CA262794-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10609917. Licensed CC0.

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