# The Role of EpCAM Glycosylation in Breast Cancer Metastasis

> **NIH NIH F30** · JOHNS HOPKINS UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT SUMMARY
Breast cancer is a widespread disease that will claim the lives of over 40,000 US women in 2022 alone, with the
majority of these deaths resulting from stage IV disease, in which cancer has metastasized to distant regions,
as metastatic disease is difficult to treat and has few effective treatment options. Breast cancer cells metastasize
by invading the basement membrane, invading into blood vessels, circulating to distant tissues, leaving the blood
vessel, and colonizing that tissue. The epithelial cell adhesion molecule (EpCAM) plays a role in cell adhesion,
migration, and invasion, and has been linked to several epithelial cancers, including breast, prostate, and
colorectal cancer. Despite its potential to facilitate several steps of the metastatic cascade and its link to epithelial
cancers, the specific role of EpCAM in metastasis remains unknown. In his study of normal tissues, primary
tumors, and metastatic nodules of 17 metastatic breast cancer patients, our collaborator Dr. Pedram Argani
determined that EpCAM protein expression was increased in metastatic nodules, without a corresponding
increase in EpCAM mRNA expression. We therefore hypothesize that post-translational modification of EpCAM,
which has three known N-glycosylation sites and no known O-glycosylation sites, stabilizes and increases the
abundance of EpCAM in metastatic tissues. Our recent study of these same samples found that the abundance
of N-glycans was significantly increased in metastatic tissues versus primary tumors versus normal tissues and
identified 25 significantly differentially abundant N-glycans of interest. Our study also found that EpCAM protein
expression was significantly increased in metastatic tissues compared to primary tumors and was significantly
statistically correlated with the expression of seven N-glycans. Taken together, these data suggest that EpCAM
N-glycosylation may play a role in metastatic progression. The central hypothesis of this project is that increases
and changes in N-glycosylation stabilize EpCAM and allow it to facilitate metastasis. I propose to test this
hypothesis through the following specific aims: Aim 1: To elucidate the impact of EpCAM N-glycosylation on
EpCAM stability and adhesion in human breast cancer cells; Aim 2: To assess the impact of EpCAM N-
glycosylation on metastasis in mouse models of breast cancer. These aims will be achieved through a
combination of cancer biology, biochemistry, and mass spectrometry approaches in human triple-negative breast
cancer cell lines and breast cancer xenograft models. This work is significant because it will elucidate the role of
N-glycosylation of EpCAM in metastatic breast cancer, determine the specific N-glycosylation profile of EpCAM
in metastasizing breast cancer cells, and may subsequently uncover novel therapeutic targets and strategies in
metastatic breast cancer.

## Key facts

- **NIH application ID:** 10833009
- **Project number:** 5F30CA268849-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Nicole Marie Jenkinson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833009

## Citation

> US National Institutes of Health, RePORTER application 10833009, The Role of EpCAM Glycosylation in Breast Cancer Metastasis (5F30CA268849-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10833009. Licensed CC0.

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