# Platelet Serine/Threonine Phosphatases in Cancer Pathophysiology

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $412,172

## Abstract

The five year survival rate for lung cancer is ~20% despite improved screening methods and advances in
treatment. Tumor metastasis is one of the major causes of death in cancer patients. Besides the dysregulated
signaling in tumor cells, the survival of dislodged circulating tumors from detachment-induced apoptosis
(anoikis) and immune attack in the blood depends on a crosstalk between the tumor and support cells in the
tumor microenvironment, including blood platelets. Lung cancer patients with high platelet count are often
associated with worst survival and a lower efficacy towards chemotherapeutic agents. Although platelets are a
determinant in tumor metastasis, current anti-platelet therapy (aspirin and clopidogrel) with an established role
in cardiovascular disease, has challenges when deployed for the management of cancer. Therefore, new
approaches to better understand the platelet-cancer crosstalk is needed to identify novel platelet targets.
Interestingly, platelets from cancer subjects have quantitative changes in the proteome. It is currently unknown
if the cancer-induced changes in platelet protein(s) merely serve as a biomarker(s) or promote disease
progression. This critical unanswered problem in the field has the potential to provide new insights into disease
mechanisms that are influenced by platelets. Recent studies suggest a role for the catalytic subunit of protein
phosphatase 1 (PP1c) in the platelet-cancer crosstalk. Our preliminary studies revealed that the platelets
isolated from human lung cancer patients and mice with experimental lung cancer show increased PP1cα
protein compared to the non-cancer controls. Importantly, conditional deletion of PP1cα in platelets showed
reduced tumor burden in an experimental model of lung cancer metastasis. Our overarching hypothesis is that
platelet PP1cα facilitates lung cancer metastasis by reducing detachment-induced apoptosis (anoikis) and/or
promoting an immunosuppressive milieu. This proposal will determine how platelet PP1cα promotes lung
cancer metastasis using novel mice models and investigators with expertise in platelet phosphatases, cancer
biology, platelet-cancer cross talk and immunology of lung cancer. In Aim 1, we will investigate the role of
platelet PP1cα in lung cancer survival and metastasis. Aim 2 will determine the role of platelet PP1cα on
immune responses to lung cancer. This work could lead to studies wherein simultaneous blockade of
platelet/extracellular PP1cα along with immune check points may provide exclusive opportunities to optimize
cancer immunotherapy.

## Key facts

- **NIH application ID:** 10360475
- **Project number:** 5R01CA247917-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** K. Vinod VIJAYAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $412,172
- **Award type:** 5
- **Project period:** 2021-03-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360475

## Citation

> US National Institutes of Health, RePORTER application 10360475, Platelet Serine/Threonine Phosphatases in Cancer Pathophysiology (5R01CA247917-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10360475. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*