# Mechanically-Activated Calcium Signaling in Breast Epithelial Cancer Cells

> **NIH NIH F31** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $1

## Abstract

Project Summary/Abstract
Early stages of breast cancer can often be treated successfully with targeted therapy, resulting a favorable
long term prognosis. However, metastatic stages are likely to manifest later on and overall survival rates drop
dramatically despite attempts for intervention using conventional chemotherapies. Due to this unmet need for
treatment of metastatic breast cancer, it will be imperative to improve our understanding of the metastatic
process so that therapeutic intervention can be designed. I will be investigating the very early stages of the
metastatic cascade, cell escape from the primary tumor. My in vitro scratch model allows for investigation of
early signaling mechanisms, such as Ca2+, in regulating the initiation of an increased migratory capacity of
breast cancer cells that drives tumor escape. Our previous work showing mechanisms underlying mechanically
sensitive Ca2+ signaling in MCF-7 cells suggests that this mechanical scratch-wounding response activates
P2Y2 receptors and resulting Ca2+ release. This study will test the hypothesis that mechanically-activated
Ca2+ signaling promotes microtubule acetylation to drive breast cancer cell migration. Although
collective evidence from the literature and new preliminary data support this hypothesis, these detailed
mechanisms linking Ca2+ and migration through microtubule post-translational modifications (MT-PTMS) have
not been shown in vitro or in vivo for breast cancer. Our approach is to first define mechanisms through which
the mechanical microenvironment effects this wounding response, by testing activation of P2Y2-Ca2+ in varying
in vitro elastic modulus conditions (Aim 1). We will then analyze increases in microtubule acetylation
downstream of P2Y2-Ca2+ and its role in enhancing capacity for cell migration in vitro (Aim 2). This wounding-
linked modulation of breast cancer cell migration will be tested in vivo by determining its effects on tumor
invasion (Aim 2). We aim to understand how changes to the mechanical environment of the cell can affect this
signaling pathway and resulting cell migration and tumor invasion. We propose that the well-established
changes in tumor rigidity and resulting abnormal cell behaviors (e.g. migration) are acting through Ca2+
signaling and MT-PTMs. New understanding of the metastatic process will be achieved through this work and
as a direct result of support through this fellowship. The training I will receive with this support will serve to
enhance my previous research experience in areas such as the development of research questions, data
analysis, and data interpretation. It will also add new training in confocal microscopy, cancer cell biology, and
mouse tumor models to my repertoire of experimental tools. In all, I will be provided with a more broad
scientific foundation to become a successful independent investigator.

## Key facts

- **NIH application ID:** 9941063
- **Project number:** 5F31CA232393-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Stephen J. P. Pratt
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2018-07-16 → 2020-07-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941063

## Citation

> US National Institutes of Health, RePORTER application 9941063, Mechanically-Activated Calcium Signaling in Breast Epithelial Cancer Cells (5F31CA232393-03). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9941063. Licensed CC0.

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