# Wnt-driven adhesion and extracellular matrix dynamics in breast cancer metastasis

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2024 · $48,974

## Abstract

Project Summary
Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype that constitutes 10%–15% of all
breast cancer cases in the United States, disproportionately affects Hispanic and African-American women.
TNBC is associated with relatively poorer outcomes than other breast cancer subtypes due to the inherently
invasive clinical behavior of TNBC and the lack of expression of molecules targeted by therapeutic agents that
are effective for other breast cancer subtypes. TNBC displays molecular and transcriptomic heterogeneity, and
both canonical (β-catenin–dependent) and noncanonical (β-catenin–independent) Wnt signaling dysfunction can
mediate TNBC progression. Our group identified an inverse correlation between canonical and noncanonical
Wnt signaling pathways, in which the noncanonical receptor, tyrosine kinase-like orphan receptor (Ror2),
spatiotemporally regulates Wnt signaling in basal-like breast cancer. More recently, our lab identified that Wnt–
Ror2 signaling can regulate tumor cell–driven extracellular matrix (ECM) modifications to support basal-like
breast cancer invasion. However, the integration of Wnt signaling cues that drive ECM remodeling and promote
colonization competence at distant sites remains unresolved. We hypothesize that Wnt signaling plasticity,
influenced by the presence or absence of Ror2, fosters adhesion and matrix alterations in the lung
metastatic niche to mediate micro-to-macrometastasis progression in TNBC. In Specific Aim 1, we will
investigate how fluctuations in Wnt signaling modulate the ECM to bolster the ability of basal-like TNBC to
colonize the lungs. Specifically, Aim 1.1 will map the dynamics of Wnt signaling transitions and monitor
associated changes in ECM composition through various metastatic stages using models of lung metastasis.
Aim 1.2 will focus on discerning alterations in the integrin–fibronectin relationship in response to genetic shifts in
Wnt signaling. In Specific Aim 2, we will determine how Wnt signaling alterations influence tumor cell
interactions with the lung endothelium, focusing on adhesion, extravasation, and macrometastatic progression
post-colonization. Aim 2.1 will assess how perturbations in Wnt–Ror2 signaling impact interactions with the
perivascular lung niche, potentially dictating patterns of basal-like TNBC tumor cell growth and arrest. Aim 2.2
will explore the role of Wnt signaling in regulating tumor dormancy cycles. Our overarching goal is to decode
how Wnt signaling variations drive the metastatic journey of TNBC within the lungs. Utilizing both in vitro and in
vivo methodologies, including genetically engineered mouse models of TNBC, we aim to unravel how Wnt–Ror2
signaling modifications affect metastatic aptitude in TNBC.

## Key facts

- **NIH application ID:** 10998319
- **Project number:** 1F31CA295013-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Erika Mendoza Mendoza
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998319

## Citation

> US National Institutes of Health, RePORTER application 10998319, Wnt-driven adhesion and extracellular matrix dynamics in breast cancer metastasis (1F31CA295013-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10998319. Licensed CC0.

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