# Stromal Fibroblast Autophagy In Tumor Progression and Desmoplasia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $328,888

## Abstract

PROJECT SUMMARY
Carcinoma progression depends on the interactions of epithelial tumor cells with their surrounding stroma.
Fibroblasts represent a principal component of this stroma, which modulates tumor cell behavior through
diverse mechanisms, including the synthesis of growth and angiogenic factors, cytokines, extracellular matrix
components and proteases. Indeed, many solid tumors exhibit striking histological evidence of fibroblast
proliferation and activation, termed desmoplasia. Although desmoplasia in human cancers tightly correlates
with poor prognosis, the molecular mechanisms that generate and maintain this desmoplastic response remain
unknown. In preliminary studies, we have uncovered that autophagy in stromal fibroblasts is crucial for
promoting both desmoplasia and tumor progression. Autophagy is a tightly regulated lysosomal degradation
process that promotes tumor cell survival and metabolic adaptation. There is great interest in targeting
autophagy against cancer due to its well-established effects on tumor cell survival; however, the potential pro-
tumorigenic functions of autophagy in the host stroma remain unknown. We hypothesize that autophagy in
stromal fibroblasts is critical to initiate and maintain a desmoplastic fibrotic response and to facilitate tumor
progression. Using powerful immune-competent mammary cancer models and tools uniquely developed in our
laboratory, we will rigorously scrutinize the functions of stromal fibroblast autophagy during cancer progression
in vivo. In Aim 1, we will determine how autophagy in stromal fibroblasts modulates tissue stiffness and ECM
remodeling. In Aim 2, we will dissect how autophagy-dependent secretion by stromal fibroblasts promotes
carcinoma progression and influences the tumor microenvironment. In Aim 3, we will corroborate the effects of
stromal fibroblast autophagy in mammary cancer progression and metastasis using autochthonous tumor
models. These studies will provide unique conceptual insight into whether and how the autophagy pathway in
host fibroblasts can be modulated to abolish the stromal response required for cancer progression.

## Key facts

- **NIH application ID:** 10058245
- **Project number:** 5R01CA213775-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jayanta Debnath
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,888
- **Award type:** 5
- **Project period:** 2017-12-13 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058245

## Citation

> US National Institutes of Health, RePORTER application 10058245, Stromal Fibroblast Autophagy In Tumor Progression and Desmoplasia (5R01CA213775-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10058245. Licensed CC0.

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