# Cell adhesion and ferroptosis: investigating a potential vulnerability in cancer cells

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $46,036

## Abstract

Project Summary
 Ferroptosis is a form of oxidative regulated necrosis caused by an inability of the
phospholipid-targeting glutathione peroxidase GPx4 to detoxify lipid hydroperoxides.
Recently, we found that E-cadherin homodimerization can regulate cell sensitivity to the
induction of ferroptosis by inhibition of glutathione synthesis or GPx4 inhibition.
Mechanistically, we found that this is due to crosstalk with the Hippo signaling pathway,
which regulates the transcriptional co-activator YAP. YAP was found to regulate the
expression of genes related to ferroptosis. E-cadherin, which is frequently mutated in
gastric cancer, is an important suppressor of motility and thus metastasis in tumors.
Intriguingly, cancer cells with a metastatic-like phenotype were found to be highly
sensitive to ferroptosis, suggesting that the loss of E-cadherin or perhaps other
adhesion molecules could play a role in regulating this process. As such, we would like
to better understand the relationship cells, their environment, and sensitivity to
ferroptosis using a variety of techniques, both in vitro and in vivo. First, we intend to
determine whether common mutations to the E-cadherin gene found in cancer patients
can render gastric cancer cells sensitive to ferroptosis. We would also like to determine
whether this phenomenon is specific to E-cadherin, or a more general cell non-
autonomous mechanism of regulation that coordinates with adjacent cells and the
extracellular matrix. Finally, we would like to determine, in mouse models of gastric
cancer, whether E-cadherin is a determinant for sensitivity to ferroptosis, and whether
the induction of ferroptosis can reduce tumor growth and metastasis.

## Key facts

- **NIH application ID:** 10213635
- **Project number:** 5F31CA247112-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Alexander Michael Minikes
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-07-07 → 2022-07-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213635

## Citation

> US National Institutes of Health, RePORTER application 10213635, Cell adhesion and ferroptosis: investigating a potential vulnerability in cancer cells (5F31CA247112-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10213635. Licensed CC0.

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