Wednesday, July 2, 2025 7/2/2025

Examining PHGDH-mediated activation of sialic acid metabolism to drive triple-negative breast cancer metastasis

Award Number: R01CA270136
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/11/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

Examining PHGDH-mediated activation of sialic acid metabolism to drive triple-negative breast cancer metastasis - PROJECT SUMMARY We recently discovered that low, rather than high, expression of phosphoglycerate dehydrogenase (PHGDH) in the serine biosynthesis pathway is indicative of metastasis in triple negative breast cancer (TNBC) primary tumors. Our preliminary experiments indicate that low PHGDH expression results in upregulation of the sialic acid biosynthesis pathway, which in turn activates cellular programs required for metastasis. However, catalytic inhibition of PHGDH does not increase sialic acid biosynthesis or metastasis, suggesting a non-catalytic role for PHGDH. This project aims to: 1) investigate this non-canonical role of PHGDH in modulating sialic acid biosynthesis, 2) decipher the metabolic rewiring that dictates low-PHGDH activation of sialic acid metabolism, and 3) elucidate the mechanism of low PHGDH, high sialic acid metabolism-driven metastasis. To confirm non- canonical PHGDH function, we will knock out other serine biosynthetic genes to show that it is not inhibition of serine biosynthesis that drives sialic acid upregulation and metastasis. We will investigate PHGDH protein- protein interactions and subcellular localization of PHGDH protein to further probe its non-canonical function. Metabolic rewiring in low-PHGDH cells will be elucidated in detail using mass spectrometry methods. We will also overexpress genes in metabolic pathways branching from glycolysis to determine whether sialic acid metabolic flux is sensitive to diversion of carbon flux into competing pathways. Finally, our preliminary data links high sialic acid metabolic flux to increased phosphorylation of EMT markers and p38 and c-SRC as drivers of metastasis. We will study the importance of p38 and SRC phosphorylation in potentiating metastasis and investigate whether this link is mediated by increased sialic acid flux or sialylation at the cell surface. Our overall objective is to elucidate the mechanism of low PHGDH driven sialic acid upregulation as an enabler of breast cancer metastasis, which will lead to new biomarkers (low PHGDH, high sialic acid) for metastasis and development of novel therapeutic strategies for metastatic 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: 2025 ( Subtotal = $363,665 )
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	4	2/14/2025	NON-COMPETING CONTINUATION	$363,665
														Subtotal = $363,665

Issue Date FY: 2024 ( Subtotal = $383,868 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	3	1/23/2024	NON-COMPETING CONTINUATION	$363,665
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	001	3	4/16/2024	NON-COMPETING CONTINUATION	$20,203
														Subtotal = $383,868

Issue Date FY: 2023 ( Subtotal = $395,991 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	2	2/27/2023	NON-COMPETING CONTINUATION	$395,991
														Subtotal = $395,991

Issue Date FY: 2022 ( Subtotal = $404,071 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	1	3/11/2022	NEW	$404,071
														Subtotal = $404,071

Grand Total All Awards = $1,547,595

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Examining PHGDH-mediated activation of sialic acid metabolism to drive triple-negative breast cancer metastasis

Award Number: R01CA270136

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/11/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer