Tuesday, December 30, 2025 12/30/2025

Role of PTPRT in colon cancer progression and metastasis

Award Number: R01CA260629
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/24/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Role of PTPRT in colon cancer progression and metastasis - Protein tyrosine phosphatase receptor T (PTPRT) is frequently mutated in human cancers, including colorectal cancer. PTPRT has two tyrosine phosphatase domains. While the membrane-proximal domain is an active protein tyrosine phosphatase, it has been thought that the C-terminal domain is a pseudo-phosphatase lacking enzymatic activity. Our preliminary data demonstrated that the pseudo-phosphatase domain of PTPRT is an active enzyme, termed denitrase, that removes nitro-groups (NO₂ at the 3-carbon position of the phenol ring of tyrosine) from the Y333 residue in ERK and Y404 residue paxillin. We demonstrated that nitro-Y333 (nY333) Erk increases its kinase activity, whereas nitro-Y404 (nY404) paxillin is likely to transduce cell signal through a “reader” (nY binding protein). Further, we generated denitrase-inactivating mutant knockin mice and showed that the mutant mice are susceptible to carcinogen-induced colon tumor development. Recently, several recent bioinformatics studies demonstrated that PTPRT mutations, including those in the denitrase domain, are enriched in metastatic colorectal cancers, suggesting that inactivation of PTPRT denitrase promotes tumor metastasis. Thus, we hypothesize that the PTPRT-regulated ERK and paxillin nitration signaling pathways play a critical role in colorectal progression and metastasis. Three aims are proposed to test this central hypothesis by determining the role of: (1) PTPRT denitrase-regulated paxillin nitration signaling in colorectal cancer progression and invasion; and (2) PTPRT denitrase-regulated Erk nitration signaling in colorectal cancer progression and metastasis. Protein tyrosine nitration is currently believed to be a byproduct of reactive oxygen/nitrogen species and not regulated by enzymes. Success in our proposed studies will establish protein tyrosine nitration as a critical player in colorectal tumor progression and metastasis.


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 = $0 )
2026	2024	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cancer Biology Research	000	3	12/16/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $881,958 )
2025	2025	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cancer Biology Research	001	4	8/14/2025	EXTENSION WITH OR WITHOUT FUNDS	$881,958
2025	2024	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cancer Biology Research	000	3	8/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $881,958

Issue Date FY: 2024 ( Subtotal = $418,930 )
2024	2024	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cancer Biology Research	000	3	7/12/2024	NON-COMPETING CONTINUATION	$418,930
														Subtotal = $418,930

Issue Date FY: 2023 ( Subtotal = $432,159 )
2023	2023	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cancer Biology Research	000	2	7/25/2023	NON-COMPETING CONTINUATION	$432,159
														Subtotal = $432,159

Issue Date FY: 2022 ( Subtotal = $440,979 )
2022	2022	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cancer Biology Research	000	1	8/24/2022	NEW	$440,979
														Subtotal = $440,979

Grand Total All Awards = $2,174,026

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Role of PTPRT in colon cancer progression and metastasis

Award Number: R01CA260629

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/24/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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