# Hormonal Regulation and Tumor Promotional Phenotypes of Semaphorin 7a in Breast Cancer

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2020 · $32,935

## Abstract

Project Summary/Abstract
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-associated
death in women in the United States. Over half of all breast cancers are hormone receptor positive (HR+), due
to their expression of the estrogen and/or progesterone receptor (ER/PR). While ER-targeted therapies are
typically successful at treating primary tumor growth, up to 40% of ER-positive tumors eventually recur and
metastasize. Therefore, novel molecular targets are needed to treat recurrent and metastatic HR+ breast
cancers. Our previous research identified Semaphorin 7a (SEMA7A) as a mediator of various aspects
associated with HR+ breast cancer progression, including proliferation, invasion, and cell survival. SEMA7A is
a signaling molecule known to drive neuronal development, immunity, and fibrosis. SEMA7A is a unique
member of the semaphorin family, as it is the only semaphorin with a GPI-anchor that can be cleaved, allowing
SEMA7A to be shed into the extracellular environment. This supports my proposal that SEMA7A may affect
the tumor microenvironment in addition to inherent cellular processes. Analysis of multiple publicity available
breast cancer patient cohorts revealed increased SEMA7A expression in breast tumors compared to normal
breast tissue, as well as a significant correlation between SEMA7A expression and decreased survival. Taken
together, this led me to hypothesize that SEMA7A promotes breast tumor progression and may be a novel
therapeutic target. However, the molecular mechanisms behind increased SEMA7A expression and how
SEMA7A signals to result in aggressive tumor cell behaviors remain unknown.
The goals of this proposal are to determine: 1) how SEMA7A expression is upregulated in HR+ breast cancer,
2) how SEMA7A signaling promotes cell survival, and 3) whether SEMA7A promotes metastasis via
remodeling of the blood vasculature. In aim 1, I will determine whether nuclear hormone receptors directly
induce transcriptional regulation of SEMA7A. I will also examine how SEMA7A signals to induce the observed
pro-survival phenotype. In aim 2, I will examine if SEMA7A promotes metastasis through blood vessel
remodeling. The expected outcomes of this research will further our understanding of SEMA7A expression and
signaling in HR+ breast cancer. These results will have a positive impact by characterizing a novel potential
therapeutic target in HR+ breast cancer. Finally, as SEMA7A is minimally expressed in most adult tissues, we
postulate this therapy will have low toxicity, making it ideal for clinical application.

## Key facts

- **NIH application ID:** 9834681
- **Project number:** 5F31CA236140-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Lyndsey S Crump
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,935
- **Award type:** 5
- **Project period:** 2018-12-06 → 2021-12-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834681

## Citation

> US National Institutes of Health, RePORTER application 9834681, Hormonal Regulation and Tumor Promotional Phenotypes of Semaphorin 7a in Breast Cancer (5F31CA236140-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9834681. Licensed CC0.

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