# NFAT activation in kGPCR tumorigenesis

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $377,438

## Abstract

Abstract
Herpesviruses are ubiquitous in humans and they have been implicated in diverse malignancies. Human
Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus are associated with tumors of
lymphoid, epithelial, and endothelial origin in immuno-compromised patients. The ability of these human
pathogens to induce tumor formation is largely attributable to oncogene(s) that the viral genome contains.
When expressed in cells, oncogenic viral polypeptides trigger cellular signaling cascades that culminate in
promoting cell proliferation and survival. One of such viral signaling molecules is the KSHV G protein-coupled
receptor (kGPCR).
kGPCR is a seven-transmembrane protein that transmits signal across the plasma membrane. Despite being a
functional homolog of the human IL-8 receptor, kGPCR is constitutively active independent of ligand binding.
One key signaling pathway downstream kGPCR is the activation of nuclear factor of activated T cells (NFAT).
However, how kGPCR regulates NFAT activation and the roles of NFAT in kGPCR tumorigenesis remain not
well understood. In particular, the kGPCR-NFAT-chemokine circuitry fuels a feed-forward outcome, implying
the existence of negative regulatory mechanisms. In this study, we propose to delineate the mechanism by
which kGPCR explores a kinase and a metabolic enzyme to negatively regulate and tune NFAT activation,
thereby promoting tumorigenesis. We will employ pharmacological agents to hyper-activate NFAT and thwart
kGPCR tumor formation. Overall, our work will decipher the signaling labyrinth and develop a new antiviral and
antitumor strategy targeting oncogenic GPCRs, instructing us on new means to treat KSHV-associated
malignancies and other diseases related to NFAT activation.

## Key facts

- **NIH application ID:** 9960451
- **Project number:** 5R01CA221521-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Pinghui Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,438
- **Award type:** 5
- **Project period:** 2017-07-31 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960451

## Citation

> US National Institutes of Health, RePORTER application 9960451, NFAT activation in kGPCR tumorigenesis (5R01CA221521-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9960451. Licensed CC0.

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