Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Impact of extracellular glutathione catabolism on triple-negative breast cancer

Award Number: R01CA269813
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/18/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027
AWARD TERMINATION DATE: 04/29/2025

Group Awards By:

View Award Description

Impact of extracellular glutathione catabolism on triple-negative breast cancer - Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with limited treatment options. There is an emerging interest in blocking antioxidants for cancer therapy, but how antioxidants promote cancer growth is unclear. Glutathione (GSH) is the most abundant antioxidant in the body and our previous work has shown that GSH promotes tumorigenesis of triple-negative breast cancers (TNBC). It is generally assumed that GSH acts intracellularly as an antioxidant in cancer cells. However, our preliminary studies show that blocking intracellular GSH synthesis does not impede TNBC growth. These surprising results suggest an alternative mechanism where extracellular GSH supports breast tumor growth. The overarching goal of this proposal is to determine how extracellular GSH promotes tumor growth. It is known that extracellular GSH is present in plasma but cells cannot import GSH. Instead, GSH is metabolized by gamma-glutamyl transferase (GGT1) to produce a glutamyl- dipeptide and cysteinylglycine, which yields cystine and glycine. Indeed, we find that ablation of GSH synthesis in vivo not only lowers circulating GSH but also reduces the levels of cysteinylglycine, cysteine, and glycine in tissues. Further, we show that supplementation with GSH and cysteinylglycine can rescue TNBC growth upon cystine depletion in GGT1-dependent and -independent manners, respectively. Together, these preliminary data suggest an alternative mechanism where GSH functions as a circulating source of metabolites rather than as a direct antioxidant. In this proposal, we describe experiments that will test the hypothesis that the catabolism of extracellular GSH by tumor GGT1 supports TNBC growth. In Aim 1, we will elucidate the impact of extracellular GSH on TNBC growth. In Aim 2, we identify the reliance of TNBC on GGT1-mediated GSH catabolism. In Aim 3, we will determine the mechanisms by which cysteinylglycine supplies cysteine for TNBC growth. Our research will challenge the paradigm of antioxidant function in cancer by describing a novel mechanism of GSH function as a circulating source of amino acids. Further, these studies have the potential to reveal a completely new set of unrealized targets and therapeutic strategies for TNBC.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $339,828 )
2026	2026	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	000	5	1/12/2026	NON-COMPETING CONTINUATION	$339,828
														Subtotal = $339,828

Issue Date FY: 2025 ( Subtotal = $442,995 )
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	004	4	6/2/2025	NON-COMPETING CONTINUATION	$37,885
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	005	4	9/24/2025	SUPPLEMENT FOR EXPANSION	$6,414
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	003	4	4/28/2025	NON-COMPETING CONTINUATION	$0
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	001	4	1/23/2025	SUPPLEMENT FOR EXPANSION	$57,718
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	000	4	1/22/2025	NON-COMPETING CONTINUATION	$340,978
2025	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	002	3	4/28/2025	TERMINATION	$0
														Subtotal = $442,995

Issue Date FY: 2024 ( Subtotal = $482,985 )
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	005	3	4/17/2024	SUPPLEMENT FOR EXPANSION	$3,206
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	003	3	4/16/2024	NON-COMPETING CONTINUATION	$19,007
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	002	3	1/29/2024	SUPPLEMENT FOR EXPANSION	$57,719
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	000	3	1/25/2024	NON-COMPETING CONTINUATION	$342,128
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	001	3	1/26/2024	SUPPLEMENT FOR EXPANSION	$57,719
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	004	3	4/16/2024	SUPPLEMENT FOR EXPANSION	$3,206
														Subtotal = $482,985

Issue Date FY: 2023 ( Subtotal = $490,005 )
2023	2023	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	004	2	7/24/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2023	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	001	2	3/31/2023	SUPPLEMENT FOR EXPANSION	$59,863
2023	2023	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	003	2	7/17/2023	SUPPLEMENT FOR EXPANSION	$49,639
2023	2023	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Cancer Biology Research	000	2	2/1/2023	NON-COMPETING CONTINUATION	$367,876
2023	2023	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Biology Research	002	2	4/28/2023	NON-COMPETING CONTINUATION	$12,627
														Subtotal = $490,005

Issue Date FY: 2022 ( Subtotal = $388,174 )
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Cancer Biology Research	000	1	4/18/2022	NEW	$388,174
														Subtotal = $388,174

Grand Total All Awards = $2,143,987

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Impact of extracellular glutathione catabolism on triple-negative breast cancer

Award Number: R01CA269813

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/18/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

AWARD TERMINATION DATE: 04/29/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer