Pumping iron: inhibition of key pathway promotes iron-dependent cell death in pancreatic cancer cells

Cell culture study maps mechanisms underlying a new potential strategy for killing pancreatic cancer cells through a type of cell death known as ferroptosis.

10:17 AM

Author | Ian Demsky

purple and blue microscopic cancer cells with lab note badge on bottom right in yellow and navy
Pancreatic cancer cells grown in culture, SEM / Anne Weston, Francis Crick Institute (CC BY-NC 4.0)

One of the reasons pancreatic cancer remains the most deadly of the major cancers is that it craftily rewires normal cell survival mechanisms to keep itself supplied with nutrients to fuel its expansion.

A new study led by the University of Michigan Rogel Cancer Center demonstrates how inhibiting a key enzyme known as GOT1 can flip a switch in the cancer cells — causing them to shift from using nutrients to fuel growth toward conserving them to maintain energy levels.

In this state, the cancer cells release their iron stores and become vulnerable to a form of programmed, iron-dependent cell death known as ferroptosis, according to findings in cell cultures that appear in Nature Communications.

"If pancreatic cancer's success comes from approaching nutrient metabolism differently than other cancers, our goal is to target aspects of that metabolism for therapeutic benefit," said study senior author Costas Lyssiotis, Ph.D., an associate professor of molecular and integrative physiology and of internal medicine at U-M.

The study was led by first author Daniel Kremer, Ph.D., a recent graduate of U-M Program in Chemical Biology and former member of the Lyssiotis lab.

The GOT1 pathway helps the cancer cells maintain their energy balance, Kremer explained.

"When we inhibit the enzyme, it doesn't kill the cell, but it puts it into a state of energetic stress, so it has to use those nutrients to maintain the cell rather than for growth," he said. "This study describes the mechanisms of that process and how we might be able to exploit it to trigger cell death through ferroptosis."

Key collaborators on the project include Yatrik Shah, Ph.D., of the Rogel Cancer Center and Kenneth Olive, Ph.D., of Columbia University and the Herbert Irving Comprehensive Cancer Center.

Paper cited: "GOT1 inhibition promotes pancreatic cancer cell death by ferroptosis," Nature Communications. DOI: 10.1038/s41467-021-24859-2


More Articles About: Lab Notes Pancreatic cancer Cancer Research All Research Topics Cancer: Cancer Types
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of healthcare news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]

734-764-2220

Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Subscribe
Featured News & Stories mutlicolored cells merging microscopic blue image with lab note badge in yellow on right
Health Lab
Cholesterol-carrying protein found to help suppress immune response in pancreatic tumor microenvironment
ApoE has known roles in cardiovascular disease and Alzheimer’s, but was not previously implicated in pancreatic cancer.
Blue image of a microscopic helix strand
Health Lab
Researchers discover urine based test to detect head and neck cancer
At-home test can detect tumor DNA fragments in urine samples, providing a non-invasive alternative to traditional blood-based biomarker tests
Photo of two silhouettes in a hallway
Health Lab
Most new doctors face some form of sexual harassment, even after #MeToo
Sexual harassment of all kinds is a common experience among first-year medical residents, also known as interns, especially those in surgical specialties, but it may be declining.
Spilled pills next to a stethoscope and pile of cash
Health Lab
Drug pricing program improved prostate cancer treatment adherence
Socially vulnerable patients were more likely to stick with oral medications when treated at a hospital participating in 340B program, suggesting these hospitals may have more resources to help patients.
Four older women pose and smile
Health Lab
Unlocking the secrets of SuperAgers
People in their 80s and 90s with cognitive abilities similar to much younger people, called super agers, are taking part in a national study of their brain health.
Animated microscopic image of the glioblastoma's tumor microenvironment
Health Lab
New model of key brain tumor feature could help scientists understand how to develop new treatments
Model shows how oncostreams form and behave in brain tumors – and how to inhibit them