# Role of breast cancer-secreted miRNA in directing a stromal metabolic plasticity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $481,850

## Abstract

PROJECT SUMMARY/ABSTRACT
The metabolic interactions and coevolution that occur between cancer and stromal cells is an unexplored topic
that combines cancer metabolism and tumor microenvironment. The proposed project will investigate this
unique aspect of cancer–host crosstalk from the novel perspective of extracellular miRNAs, whose function in
transferring cancer-derived signals to various types of niche cells to facilitate cancer growth and metastasis
has been recently recognized. MiRNA negatively regulates gene expression through inducing mRNA
degradation and/or translation blockade. The goals of this study are to identify the mechanisms by which
cancer cell-secreted miRNAs direct a metabolic plasticity in stromal fibroblasts to engage different
modes of cancer–stroma interactions under different metabolic conditions, and to examine potential
therapeutic interventions targeting this process. In Aim 1, we will determine the acting mechanisms of
selected breast cancer (BC)-secreted miRNAs in the metabolic reprogramming of cancer-associated
fibroblasts (CAFs), including a mechanism through activation of MYC-directed metabolic program. In Aim 2, we
will characterize the metabolic interplays between BC cells and reprogrammed CAFs under different metabolic
conditions using stable isotope tracing and cell co-cultures. The specific role of selected miRNAs as well as
their target genes will be determined by genetic modifications and pharmacological inhibition. In Aim 3, we will
evaluate the in vivo effects of the herein identified miRNA-regulated pathways, as well as their pharmacological
inhibition, on tumor growth and progression using models of co-transplanted BC and CAF cells derived from
patients. We will also examine the associations among selected miRNAs and metabolic genes/regulators in
human BCs, as well as the circulating levels of these miRNAs in the corresponding serum samples. The
proposed studies will provide a novel perspective to our understanding of the dynamic communication between
cancer and host as well as cancer's response to metabolic therapies, and will establish rationales for novel
therapeutic strategies to slow or stop BC progression, which is our long-term objective. Clinical-stage inhibitors
will be examined for their effects to block cancer–stroma metabolic interactions and suppress tumor
progression, which allows rapid translation into future clinical trials.

## Key facts

- **NIH application ID:** 9983643
- **Project number:** 5R01CA218140-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Shizhen Emily Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $481,850
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983643

## Citation

> US National Institutes of Health, RePORTER application 9983643, Role of breast cancer-secreted miRNA in directing a stromal metabolic plasticity (5R01CA218140-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9983643. Licensed CC0.

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