# (PQ5) Microenvironmental Regulation of Mitochondrial Heterogeneity in Cancer Metastasis

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $423,962

## Abstract

ABSTRACT
Metastasis accounts for more than 90% of all cancer deaths. The underlying mechanisms controlling the
metastatic cascades are still poorly understood. Mitochondrial metabolism has emerged as a key component
and potential master regulator of cancer metastasis, and increased mitochondrial activities have been observed
in circulating tumor cells. We have previously developed a micropatterned tumor-stromal assay (µTSA) to
recapitulate spatially-resolved cellular cross-talks at the tumor-stroma interface in breast cancer, and we recently
discovered that heterogeneous mitochondrial phenotypes are induced near the tumor-stroma interface. Our
central hypothesis is that physicochemical interactions in tumor microenvironment give rise to heterogeneous
mitochondrial and metabolic activities, leading to differential invasive and metastatic phenotypes. Here we will
develop µTSA-based tumor models to mimic critical tumor microenvironmental cues, and to evaluate their roles
in regulating mitochondrial heterogeneity and metastatic potential both in vitro and in vivo. The proposed study
will provide not only a systems understanding of the microenvironmental determinants of mitochondrial
heterogeneity, but also the mechanistic relationship between mitochondrial and metastatic phenotypes. The
insights and developed platform will advance targeted therapeutics for cancer metastasis, and benefit a broad
range of areas including cancer metabolism, stem cell biology, biomarker discovery, and drug screening.

## Key facts

- **NIH application ID:** 10693122
- **Project number:** 5R01CA220012-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Keyue Shen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $423,962
- **Award type:** 5
- **Project period:** 2019-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693122

## Citation

> US National Institutes of Health, RePORTER application 10693122, (PQ5) Microenvironmental Regulation of Mitochondrial Heterogeneity in Cancer Metastasis (5R01CA220012-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10693122. Licensed CC0.

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