# METABOLOMIC ANALYSES OF HER2-POSITIVE BREAST CANCER CELLS

> **NIH NIH SC3** · CALIFORNIA STATE UNIVERSITY FRESNO · 2020 · $105,000

## Abstract

PROJECT SUMMARY
The oncogenic receptor, HER2, is overexpressed in 25-30% of breast cancer patients and is characterized by
aggressive growth, increased disease recurrence, and poor prognosis. While much of the signaling
mechanism(s) have been elucidated, the impact of HER2 positivity on cellular metabolism is not well
understood. Recently, we found high intracellular accumulation of lactate that correlated with HER2 positivity in
breast cancer cells. Lactate accumulation within tumor tissue is well known (Warburg effect) and largely due to
the increased glycolytic rate of cancer cells. The major lactate dehydrogenase enzymes (LDHA and LDHB) are
responsible for conversion of pyruvate to lactate and often overexpressed in cancer. This evidence points to
the alarming clinical problem: is HER2 positivity a driver towards derailed metabolism and a potentially more
proliferative/aggressive phenotype? We hypothesize that HER2 expression is the driver for a glycolytic
phenotype in a subset of breast cancer that leads to lactate accumulation. We propose three interlinked aims
to systematically define the biochemical impact of HER2 overexpression to drive breast cancer cell survival
through identifying and tracking key metabolites in the glycolytic pathway of lactate, and understand how anti-
HER2 strategies promote cell death in specific experimental cellular contexts: 1) determine the metabolic path
of lactate in HER2-positive breast cancer cells, 2) determine the metabolic impact of anti-HER2 strategies, and
3) define target candidate expression in altered metabolic pathways. A combination of 3D/spheroid breast
cancer models with variable and inducible HER2 expression will be used with metabolic tracers (13C)-glucose, -
lactate, -glutamine to define consumption and release profiles over time by unbiased, data-driven NMR
spectroscopy. This proposal is significant because it seeks to reveal the molecular mechanism between HER2
and lactate using a metabolomic approach in a robust isogenic 3D culture. Outcomes may directly impact the
selection of protein and small molecule pharmacologic tools to better understand lactate shuttling in human
malignancies. Furthermore, this is responsive to the limited scope, URM student studies targeted for the SC3
initiative and it is imperative for the critical path to show proof-of-concept with in vitro-based spheroid studies
before translating into advanced models such as human breast cancer samples.
.

## Key facts

- **NIH application ID:** 9973195
- **Project number:** 5SC3GM122630-04
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY FRESNO
- **Principal Investigator:** Jason Allan Bush
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $105,000
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973195

## Citation

> US National Institutes of Health, RePORTER application 9973195, METABOLOMIC ANALYSES OF HER2-POSITIVE BREAST CANCER CELLS (5SC3GM122630-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9973195. Licensed CC0.

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