# Mechanisms of Ferroptotic Cancer Cell Death

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $376,282

## Abstract

Abstract
 Ferroptosis is a recently recognized form of regulated cell death driven by lipid peroxidation. It is an emerging
field in cancer biology, and the detailed molecular regulators of ferroptosis are largely unknown. We recently
demonstrated that upregulation of metallothionein (MT)-1G expression contributes to ferroptosis resistance in
human hepatocellular carcinoma cells, whereas inhibition of MT-1G expression enhances ferroptosis sensitivity
in vitro and in vivo (Hepatology. 2016 63(1):173-184.; Hepatology. 2016 64(2):488-500.). These exciting findings
raise several important questions regarding the previously unidentified role of MT-1G in the regulation of
ferroptotic cancer cell death. Our central hypothesis is that expression and release of MT-1G limits ferroptotic
cancer cell death. To test this hypothesis, we will exploit molecular, cellular, and animal models to pursue the
following aims. Aim 1: Define the mechanism responsible for transcriptional regulation of MT-1G expression in
ferroptosis. Aim 2: Define the mechanism responsible for phosphorylation modification of MT-1G function in
ferroptosis. Aim 3: Define the mechanism responsible for extracellular activity of MT-1G in ferroptosis. The
completion of these exciting studies will improve our understanding of the cancer molecular pathobiology of
ferroptosis and guide future development of novel MT-1G-based anticancer therapeutic strategies.

## Key facts

- **NIH application ID:** 10017944
- **Project number:** 5R01CA229275-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Daolin Tang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,282
- **Award type:** 5
- **Project period:** 2019-09-13 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017944

## Citation

> US National Institutes of Health, RePORTER application 10017944, Mechanisms of Ferroptotic Cancer Cell Death (5R01CA229275-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017944. Licensed CC0.

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