# Role of PTPRT in colon cancer progression and metastasis

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $418,930

## Abstract

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.

## Key facts

- **NIH application ID:** 10893342
- **Project number:** 5R01CA260629-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Zhenghe Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $418,930
- **Award type:** 5
- **Project period:** 2022-08-24 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893342

## Citation

> US National Institutes of Health, RePORTER application 10893342, Role of PTPRT in colon cancer progression and metastasis (5R01CA260629-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10893342. Licensed CC0.

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