# New perspective on MyoD function and differentiation in rhabdomyosarcoma

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $361,369

## Abstract

ABSTRACT
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents in the United
States. While generally very treatable, advanced RMS often proves resistant to treatment and results in poor
survival. RMS is linked to a muscle lineage and is believed to result, at least in part, from a failure of the
transcription factor MyoD to functionally promote terminal differentiation. Our laboratory has long studied the
role of NF-κB as a regulator of skeletal muscle differentiation, and has shown that active NF-κB prevents the
maturation of muscle, which is relevant in a number of diseases, including RMS. Because NF-κB is known to
play an important role in the ability of a number of cancers to resist cell death, we examined whether NF-κB
would have the same cell survival activity in RMS cells as a potential mechanism of chemoresistance.
Interestingly, RMS cells depleted of NF-κB remained resistant to stress. This finding led us to uncover that
RMS cells depend upon MyoD for cell survival. Further, we have determined that this MyoD-mediated
resistance to cell death occurs through a novel transcriptional repressive function of MyoD. The goal of our
project is to explore a potential new function of MyoD as a cell survival factor in the progression of RMS and
unravel the manner in which MyoD is acting to repress gene transcription, potentially relevant to RMS
pathogenesis. Because the current paradigm of future RMS treatments is to promote cell differentiation
through stimulation of MyoD, our current findings paired with our proposed aims have the potential to alter
future RMS therapies.
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## Key facts

- **NIH application ID:** 10066322
- **Project number:** 5R01CA235074-03
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Denis C Guttridge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $361,369
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066322

## Citation

> US National Institutes of Health, RePORTER application 10066322, New perspective on MyoD function and differentiation in rhabdomyosarcoma (5R01CA235074-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10066322. Licensed CC0.

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