# A DUAL ROLE OF INTEGRIN ALPHA-3 IN BREAST CANCER CNS METASTASIS & CHEMORESISTANCE

> **NIH NIH F31** · DUKE UNIVERSITY · 2022 · $35,335

## Abstract

ABSTRACT
Integrins serve a multifaceted role in cancer progression by regulating cell migration as well as
mediating signaling pathways important in proliferation and chemoresistance. Our lab was the first to
demonstrate that leukemia cells use a neural stem cell migratory pathway to invade the central nervous
system (CNS) by migrating along the abluminal surface of blood vessels that traverse the bone marrow
and leptomeninges (LM). We showed that this process was mediated by leukemia cell integrin α6
engaging laminin in the basement membrane surrounding these vessels. Similar to leukemia, breast
cancer metastasis to the LM results in severe morbidity and is a rapidly fatal complication. My
preliminary data suggest that breast cancer cells utilize both α6 and α3 integrin-laminin interactions to
invade the LM. I have also observed that breast cancer cells plated on laminin exhibit resistance to the
chemotherapeutic doxorubicin. Integrin α6 KO does not sensitize the cells to chemotherapy leading me
to hypothesize that integrin α3 serves a multifaceted role by activating chemoprotective signaling
pathways upon laminin engagement. In this research grant, I propose to more fully define the role of
α3 integrin-laminin interactions in regulating triple negative breast cancer LM metastasis along
emissary vessels and in promoting chemoresistance in the metastatic microenvironment.

## Key facts

- **NIH application ID:** 10437633
- **Project number:** 5F31CA257758-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Andrew Whiteley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $35,335
- **Award type:** 5
- **Project period:** 2021-07-01 → 2023-05-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437633

## Citation

> US National Institutes of Health, RePORTER application 10437633, A DUAL ROLE OF INTEGRIN ALPHA-3 IN BREAST CANCER CNS METASTASIS & CHEMORESISTANCE (5F31CA257758-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10437633. Licensed CC0.

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