# Roles of Hsp47 in Breast Cancer Progression

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2024 · $345,206

## Abstract

Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and poor survival
outcomes. One feature of obese adipose tissue is the excess extracellular matrix (ECM)
deposition/remodeling in the form of fibrosis. However, function and regulation of obesity-related ECM
deposition/remodeling in cancer progression largely remain to be determined. We recently identified
Hsp47, a chaperone protein facilitating collagen secretion, as a hub of the ECM transcription network.
Our new data showed that Hsp47 was highly expressed in adipose tissue. Importantly, increased Hsp47
expression in human and mouse adipose tissues was significantly associated with obesity
development. We found that adipocyte-specific deletion of Hsp47 was sufficient to suppress high fat
diet (HFD)-induced obese and mammary tumor growth, which is accompanied by reduced collagen
deposition/alignment and macrophage infiltration in adipose tissue. The overall objective of this
proposal is to define the mechanism by which adipocyte Hsp47 promotes obese-related fibrosis and
breast cancer progression and to explore the value of Hsp47 as a potential target to suppress obesity-
associated cancer progression. Using unbiased proteomics analysis, we identified asporin as a new
target of Hsp47 in adipocytes. Based on these data, the central hypothesis of this proposal is that
Hsp47 induces obesity-related fibrosis by facilitating asporin secretion in adipocytes, and subsequently
enhances adipocyte plasticity and breast cancer progression. Following aims are proposed to test our
hypothesis: Aim 1. Elucidate the molecular mechanism by which adipocyte Hsp47 induces obesity- and
cancer-associated ECM remodeling; Aim 2. Determine how Hsp47 regulates obesity-associated and
cancer-induced adipocyte plasticity; Aim 3. Define the potential of targeting Hsp47 to suppress obesity-
associate fibrosis, inflammation, and breast cancer progression/metastasis.

## Key facts

- **NIH application ID:** 10839419
- **Project number:** 5R01CA207772-08
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ren Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $345,206
- **Award type:** 5
- **Project period:** 2017-03-03 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839419

## Citation

> US National Institutes of Health, RePORTER application 10839419, Roles of Hsp47 in Breast Cancer Progression (5R01CA207772-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10839419. Licensed CC0.

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