# Metabolic reprogramming in breast cancer

> **NIH NIH R01** · RBHS -CANCER INSTITUTE OF NEW JERSEY · 2022 · $356,438

## Abstract

Summary/Abstract
As a multifunctional cytokine, LIF has a complex role in tumorigenesis. While LIF inhibits leukemia, recent
studies including ours show that LIF promotes the development and progression of many types of solid tumors,
including breast cancer. LIF is frequently overexpressed in breast cancers (~50-60%) across different
subtypes, and is enriched in breast cancers in women younger than 45, which tend to be more aggressive with
less treatment options. LIF overexpression is associated with poor prognosis. However, the precise role of
LIF in breast cancer is not well-established and its underlying mechanism is poorly understood. Metabolic
reprogramming is a hallmark of cancer cells and a key contributor to cancer progression, including breast
cancer. Enhanced glycolysis and enhanced lipid synthesis are two key metabolic changes in cancer, including
breast cancer, which are critical for cancer progression. Our preliminary studies using an unbiased approach
(liquid chromatography/mass spectrometry-based metabolite analysis) identified LIF as a novel and unique
driver for metabolic reprogramming in breast cancer. We found that: 1) LIF activates glycolysis and lipid
synthesis in breast cancer cells in vitro and in vivo; 2) blocking glycolysis and lipid synthesis by RNAi and
specific pharmacological inhibitors largely abolished the promoting effect of LIF on breast tumorigenesis.
Based on our preliminary results, we hypothesize that LIF plays a critical role in breast tumorigenesis, and
enhanced glycolysis and lipid synthesis is a critical underlying mechanism, which can be targeted for therapy.
To test this hypothesis, we proposed a rigorous research plan with robust and unbiased methods. We will 1)
establish LIF's role in breast tumorigenesis by using 3 mouse models, including LIF transgenic and knockout
mouse models; 2) determine whether metabolic reprograming driven by LIF, is a critical mechanism whereby
LIF promotes breast tumorigenesis; 3) assess the therapeutic potential of targeting these metabolic changes in
breast cancer with LIF overexpression. The goal of this study is to determine the role and mechanism of LIF in
breast cancer and metabolic reprogramming to provide effective therapeutic targets/strategies for breast
cancer. If successful, this study will: 1) provide evidence that LIF promotes breast tumorigenesis; 2) uncover
LIF as an important and unique driver for metabolic reprogramming in breast cancer; 3) reveal mechanisms for
LIF in breast tumorigenesis and metabolic reprogramming; 4) provide the rationale and strategies to target
specific metabolic changes in breast cancers with LIF overexpression.

## Key facts

- **NIH application ID:** 10349487
- **Project number:** 5R01CA227912-05
- **Recipient organization:** RBHS -CANCER INSTITUTE OF NEW JERSEY
- **Principal Investigator:** Zhaohui Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $356,438
- **Award type:** 5
- **Project period:** 2018-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349487

## Citation

> US National Institutes of Health, RePORTER application 10349487, Metabolic reprogramming in breast cancer (5R01CA227912-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10349487. Licensed CC0.

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