# Oncogenic Chromatin Remodeling and Anticancer Mechanisms

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $430,416

## Abstract

ABSTRACT
The SWI/SNF chromatin remodeling complexes impart epigenetic regulation and control accessibility of
chromatin to transcriptional machineries. Chromatin remodeling plays important roles in normal physiology and
diseases, particularly cancer. ARID1A is a component of the BAF SWI/SNF complex and a major tumor
suppressor. ARID1A is inactivated by somatic mutations in a wide spectrum of cancer types. Despite the
apparent importance of SWI/SNF chromatin remodelers in cancer, their regulation by growth and oncogenic
signals remains not well understood. mTOR complex 1 (mTORC1) is a conserved protein kinase and a central
growth controller. mTORC1 is an oncogenic driver and the target of US FDA-approved oncology drugs
rapamycin and rapamycin analogs. Our preliminary data revealed that mTORC1 promotes proteasomal
degradation of ARID1A protein. Moreover, ARID1A plays an important role in therapeutic response and
resistance to mTORC1 inhibitors. Because mTOR pathway is estimated to be activated in nearly half of all human
tumors, mTOR-dependent degradation represents a common mechanism to inactivate the ARID1A tumor
suppressor in cancer. Therefore, it is important to understand the underlying regulatory mechanisms and its role
in cancer biology and therapy. There are two specific aims in this application: Aim 1 will dissect the molecular
mechanism by which mTORC1 regulates ARID1A and oncogenic chromatin remodeling. Aim 2 will investigate
the significance of mTORC1-dependent ARID1A regulation in tumorigenesis and anticancer drug response. Our
studies are anticipated to fill a knowledge gap in the regulation of the ARID1A tumor suppressor in tumorigenesis
and anticancer drug response/resistance. If successful, this project could lead to better strategies to target mTOR
pathway, improving clinical outcomes for cancer patients.

## Key facts

- **NIH application ID:** 10862589
- **Project number:** 5R01CA280177-02
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** STEVEN ZHENG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $430,416
- **Award type:** 5
- **Project period:** 2023-06-08 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862589

## Citation

> US National Institutes of Health, RePORTER application 10862589, Oncogenic Chromatin Remodeling and Anticancer Mechanisms (5R01CA280177-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862589. Licensed CC0.

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