# Investigation of STAT2 Signaling in the tumor microenvironment

> **NIH NIH R03** · TEMPLE UNIV OF THE COMMONWEALTH · 2024 · $70,770

## Abstract

SUMMARY
Intercellular communication between tumor cells and stromal cells of which major components are
fibroblasts play a significant role in tumor growth, cancer progression and metastasis. This proposal
aims to investigate the role of STAT2 signaling in the exchange of communication between colorectal
cancer (CRC) cells and stromal cancer-associated fibroblasts (CAFs) in the tumor microenvironment.
Our preliminary show that a clinical correlation between high STAT2 expression and poor survival as
well as a positive correlation between STAT2 and markers of CAFs. Analysis of tumor biopsies of CRC
patients showed elevated STAT2 protein in the tumor and surrounding stroma. Studies in two animal
models of CRC reveal that STAT2 is tumorigenic. RNA-Seq analysis exposed a transcriptional signature
associated with tumor associated fibroblasts. Furthermore, we found that STAT2 facilitates the
proliferation and invasion of tumor cells. In parallel, we found that induction of EGF expression in normal
fibroblasts was poorly induced after incubation with conditioned medium from STAT2 deficient tumor
cells. Given these observations, we postulate that STAT2 mediates the crosstalk between the
tumor and CAFs leading to CRC disease progression. The objective is to: (1) Determine whether
intrinsic tumor STAT2 signaling leads to reprogramming of normal fibroblasts to CAFs to promote tumor
growth and (2) Determine whether STAT2 signaling in normal fibroblasts leads to their conversion to
CAFs to enhance tumor growth. Completion of this study will reveal the importance of STAT2 signaling
in the tumor microenvironment as the communication axis (unidirectional vs. bidirectional) between
tumor cells and CAFs to enhance tumor growth, migration, and invasion.
Significance: Treatment of advanced CRC by combining targeted therapies with chemotherapy has
produced modest success. Delineating the oncogenic role of STAT2 signaling in the tumor
microenvironment may lead to the development of novel therapeutic strategies. If results from our study
reveal that STAT2 plays a dynamic role in the establishment of cell-to-cell communication in the tumor
microenvironment, our findings will support a rationale to inhibit STAT2 signaling as a therapeutic
intervention for the treatment of metastatic CRC.

## Key facts

- **NIH application ID:** 10993770
- **Project number:** 3R03CA273613-02S1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** ANA M GAMERO
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $70,770
- **Award type:** 3
- **Project period:** 2023-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993770

## Citation

> US National Institutes of Health, RePORTER application 10993770, Investigation of STAT2 Signaling in the tumor microenvironment (3R03CA273613-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10993770. Licensed CC0.

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