# The role of AMPK and CD36 in breast cancer tumorigenesis and metastasis

> **NIH VA I01** · JESSE BROWN VA MEDICAL CENTER · 2022 · —

## Abstract

Breast cancer is the most frequently occurring cancer in women. Military women are at increased risk of
breast cancer. The mortality and morbidity from breast cancer is due to its metastatic spread. The role of
AMPK in tumorigenesis is controversial. Although AMPK inhibition was implicated in promoting
tumorigenesis, we showed, several years ago, that AMPK activation is required for tumor cells survival
during solid tumor formation. In recent years this assertion was independently corroborated by others in
various types of cancer. In this grant application we propose that AMPK and its downstream effector the
fatty acid translocase, CD36, are required for breast cancer metastasis. It is known that high ROS levels
in disseminating cells is an impediment for metastasis and therefore the metabolic rewiring of key
signaling pathways is critical to confer enhanced antioxidant metabolism to overcome this hurdle.
Combating high ROS levels during metastatic colonization requires increased glucose uptake and
utilization. We propose that the excess of ROS levels in disseminating breast cancer cells is a
consequence of impaired glucose uptake and utilization. This impairment inhibits the oxidative pentose
phosphate pathway (oxPPP) that generates NADPH to combat ROS. The limited glucose utilization
during dissemination also leads to the activation of AMPK. By inhibiting fatty acid synthesis (FAS) and by
elevating fatty acid oxidation (FAO), AMPK could maintain intracellular NADPH levels to combat ROS
even when glucose utilization is impaired. In the first part of this grant application we will delineate the
mechanism by which AMPK activation is required for breast cancer metastasis. In the second part of the
grant application we will determine if the fatty acid translocase, CD36, is required for tumorigenesis and
metastasis mediated by AMPK activation, and whether CD36 could be systemically targeted to inhibit
breast cancer metastasis. We will use human breast cancer cell lines and PDOs and orthotopic
transplantation as well as a mouse models for breast cancer metastasis in these studies. The proposed
studies have a translational impact as they will determine whether drug therapy that activates AMPK
directly or indirectly could have worse outcomes with respect to breast cancer metastasis, and whether
targeting CD36 could inhibit breast cancer metastasis particularly in obese patients.

## Key facts

- **NIH application ID:** 10377328
- **Project number:** 5I01BX005092-02
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** Nissim Hay
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377328

## Citation

> US National Institutes of Health, RePORTER application 10377328, The role of AMPK and CD36 in breast cancer tumorigenesis and metastasis (5I01BX005092-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10377328. Licensed CC0.

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