# Mechanistic investigation of malignant rhabdoid childhood tumor using the Drosophila model

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $347,700

## Abstract

PROJECT SUMMARY
Malignant rhabdoid tumors (MRTs) are especially lethal cancers that arise predominantly in
infancy and early childhood. Previous studies revealed that loss of SMARCB1, also known as
hSNF5/INI1, is essentially the sole recurrent event in this pediatric cancer. Since
SMARCB1/hSNF5/INI is a component of the SWI/SNF chromatin-remodeling complex, the
cause of MRTs is generally related to defective chromatin configuration. However, mutations of
other SWI/SNF complex components have not been found in MRTs, even though they are
prevalent in various adult cancers, suggesting SMARCB1 has a different role to other core
components of the SWI/SNF complex. The mechanisms through which loss of SMARCB1
causes MRTs thus remains largely unclear. In a recent study using the genetically tractable
Drosophila model system, we found that fly SMARCB1 homolog Snr1, but not other
components of the SWI/SNF complex, acts as a tumor suppressor in imaginal epithelial tissues.
We further suggested that Snr1 prevents tumorigenesis by maintaining normal endosomal
trafficking-mediated signaling network through its cytoplasmic function. On the basis of these
findings, we will continue to explore the mechanisms underlying Snr1 in tumorigenesis. The
central hypothesis in this proposal is that cytoplasmic function of Snr1 plays a major tumor-
suppressing role, whereby disruption of cytoplasmic function of Snr1 causes trafficking defects,
which leads deregulation of multiple growth-related signaling pathways either cell-autonomously
or non-autonomously, and the interaction between snr1-depleted neoplasm and neighboring
hyperplasia in the wildtype tissue results in rapid progress of tumorigenesis. We will test this
hypothesis by pursuing the following specific aims: (1) To determine how the cytoplasmic Snr1
is involved in membrane trafficking. (2) To determine how loss-of-snr1 results in neoplastic
overgrowth cell-autonomously. (3) To determine the mechanisms of non-autonomous
overgrowth upon mosaic loss of snr1. The significance of our proposed studies lies in their
implications related to understanding mechanisms of Snr1 in tumorigenesis, and scientific fields
such as cell biology, developmental biology, and cancer biology. The use of a genetic tractable
system to determine the unconventional function of Snr1 in tumor suppression will provide
insights into how loss of this pleiotropic gene can end up with a malignant pediatric cancer, and
ultimately propel the development of new therapeutic avenues against MRTs.

## Key facts

- **NIH application ID:** 10215434
- **Project number:** 5R01CA224381-04
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Wu-Min Deng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $347,700
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215434

## Citation

> US National Institutes of Health, RePORTER application 10215434, Mechanistic investigation of malignant rhabdoid childhood tumor using the Drosophila model (5R01CA224381-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10215434. Licensed CC0.

---

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