# Par-4 Regulation of Actomyosin Contractility as a Tumor Suppressive Mechanism in Breast Cancer

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $625,273

## Abstract

Project Summary/Abstract
Tumor progression – including resistance to therapy, metastasis, and recurrence – is responsible for the
majority of cancer deaths. Understanding how cancer cells survive treatment, spread to distant sites, persist
as dormant residual cells, and eventually recur is essential to improving the treatment of this disease. The
long-term goal of my research group is to identify the pathways that regulate these processes in order to
prevent or treat tumor recurrence.
To achieve, this we are using conditional genetically engineered mouse (GEM) models of breast cancer that
allow for the mechanistic dissection of the processes of dormancy and recurrence. Using these models, we
have identified a functional role for the tumor suppressor Par-4 in regulating survival and recurrence of breast
cancer cells after therapy. Par-4 is downregulated in recurrent tumors from three GEM models, and this
downregulation is both necessary and sufficient for tumor recurrence. Similarly, in women with breast cancer,
low Par-4 expression is associated with a poor response to neoadjuvant therapy and an increased risk of
recurrence. We have characterized the upstream pathways that regulate Par-4 expression and function during
dormancy and recurrence, as well as the downstream pathways that Par-4 regulates to inhibit dormant cell
survival and recurrence.
This proposal will build on this work to further explore the mechanism by which Par-4 acts as a tumor
suppressor. The overarching hypothesis of the proposal is that Par-4 promotes cell death in part through
inducing actomyosin contractility, and this contributes to its tumor suppressive functions. We will explore this
hypothesis in the context of Par-4’s role in residual cell survival and the survival of invasive lobular cancer
cells. Our work will reveal new information on how Par-4 functions to regulate dormant residual cell survival
and may uncover novel opportunities for therapeutic intervention in eliminating residual cells and preventing
recurrence.

## Key facts

- **NIH application ID:** 10770274
- **Project number:** 1R01CA285322-01
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** James V Alvarez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $625,273
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770274

## Citation

> US National Institutes of Health, RePORTER application 10770274, Par-4 Regulation of Actomyosin Contractility as a Tumor Suppressive Mechanism in Breast Cancer (1R01CA285322-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10770274. Licensed CC0.

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