# Spatial regulation of mechanistic target of rapamycin complex 1 (mTORC1) and its role in oral squamous cell carcinoma

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $41,976

## Abstract

Project Summary
Mechanistic target of Rapamycin (mTOR) complex 1 (mTORC1) integrates inputs from multiple pathways and
senses diverse signals to regulate cell growth, protein translation, and proliferation1,2. Given that spatial
compartmentalization can enhance signaling specificity and efficiency3,4, spatial regulation of mTORC1 appears
to be critical for this multifaceted signaling complex5 as it has been reported at many subcellular locations6–9.
For example, mTORC1 at the lysosome is regulated by both amino acids and growth factors and functions to
promote translation and suppress autophagy10. The complex has also been identified at peroxisomes, where
mTORC1 responds to reactive oxygen species7. However, the roles of mTORC1 at other subcellular locations
where its presence has been reported, in particular in the nucleus, are not well understood. A major limitation in
the field is the availability of tools to assess the activity and function of spatially compartmentalized signaling
enzymes in living cells. Using a genetically encoded fluorescent biosensor to monitor mTORC1 activity, the
Zhang lab has previously discovered a pool of nuclear mTORC1, which has yet to be defined in function. Based
on our preliminary data, we hypothesize that nuclear mTORC1 regulates pro-inflammatory transcription. We will
test this hypothesis by combining targeted inhibition of mTORC1 with a phosphoproteomics experiment and
biochemical assays. Lastly, since genetic mutations activating phosphoinositide 3-kinase(PI3K)/protein kinase
B (Akt)/mTOR signaling are prominent alterations in oral squamous cell carcinoma (OSCC)11,12 and mTORC1
inhibition can induce tumor regression13,14, we will study the role of subcellular mTORC1 signaling in the growth
and drug resistance of OSCC cells in vitro and in vivo in mice. We hypothesize that inhibiting mTORC1 in the
nucleus or the cytosol will differentially effect cell growth and EGFR inhibitor resistance in OSCC. The proposed
project will elucidate the function of the previously undefined pool of nuclear mTORC1 and clarify the roles of
subcellular mTORC1 in the growth and drug resistance of OSCC.

## Key facts

- **NIH application ID:** 10917109
- **Project number:** 5F31DE032886-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Ayse Zisan Sahan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,976
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917109

## Citation

> US National Institutes of Health, RePORTER application 10917109, Spatial regulation of mechanistic target of rapamycin complex 1 (mTORC1) and its role in oral squamous cell carcinoma (5F31DE032886-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10917109. Licensed CC0.

---

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