# Ferroptosis, Cellular Metabolism, and Cancer

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $415,237

## Abstract

Ferroptosis, Cellular Metabolism, and Cancer
Summary
 Programmed cell death plays important roles in normal biology, and its deregulation impacts various
human diseases, including cancer. Recent progress has established that in addition to apoptosis, which is the
best-established mode of programmed cell death, there are also other forms of programmed cell death.
Ferroptosis is a newly emerged programmed necrosis process that is implicated in multiple biological and
pathological conditions. However, its precise mechanism and function are not well understood.
 The overall goal of this proposal is to investigate the molecular basis of ferroptosis and its potential
involvement in cancer. This proposal is based on our recent finding that induction of ferroptosis requires the
extracellular iron-carrier protein transferrin and the intracellular metabolic process glutaminolysis; and inhibition
of glutaminolysis, presumably via blocking ferroptosis, reduces heart injury triggered by ischemia-reperfusion.
Because both transferrin and glutaminolysis are crucial for cancer cell viability, our finding that they are
involved in the induction of a specific type of cell death is conceptually intriguing and unexpected. Additionally,
our preliminary studies indicate that execution of ferroptosis requires active mitochondrial function, further
underscoring the intimate relationship between ferroptosis and cellular metabolic and redox machineries.
Lastly, we identified the oncogene product MYC, a master regulator of cellular metabolism and mitochondrial
function, as a positive regulator of ferroptosis.
 Based on these preliminary results, in this proposal, we will further study the molecular basis of ferroptosis
by focusing on the role and functional interplay of glutaminolysis, iron signaling, and mitochondria, in
ferroptosis (Aims-1 & 2). We will also investigate the cancer relevance of ferroptosis. Particularly, as many
cancer cells possess MYC overexpression and high levels of glutaminolysis, thus likely to be more susceptible
to ferroptosis, can we exploit this property of cancer cells (Achilles heel) to develop ferroptosis-based cancer
therapies? Experiments proposed in Aim-3 are expected to provide insights into this cancer-relevant question.

## Key facts

- **NIH application ID:** 9852427
- **Project number:** 5R01CA204232-04
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Xuejun Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,237
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852427

## Citation

> US National Institutes of Health, RePORTER application 9852427, Ferroptosis, Cellular Metabolism, and Cancer (5R01CA204232-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9852427. Licensed CC0.

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