# Roles of Hsp47 in breast cancer progression

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2021 · $344,269

## Abstract

Despite recent advance in early diagnosis and adjuvant therapy, treatment of triple negative breast
cancer (TNBC) remains a significant challenge because of the high incidence of metastasis and relapse after
treatment. Signaling from extracellular matrix (ECM), an essential component of the tumor microenvironment,
is required for TNBC progression and metastasis. However, it is not known how cancer cell-deposited ECM
proteins and ECM signaling in cancer cells are regulated and promote TNBC metastasis/relapse. We recently
identified Hsp47 as a hub of the ECM transcription network. Hsp47 is a molecular chaperon that regulates
secretion and deposition of ECM proteins. Increased Hsp47 expression has been detected in TNBC and is
associated with cancer metastasis. Silencing Hsp47 restrains the aggressive phenotype of TNBC cells in 3D
culture and inhibits tumor growth and lung colonization in the xenograft model, indicating that increased Hsp47
expression is crucial for the TNBC progression. EMT promotes cancer progression by enhancing cancer cell
dissemination and endowing cancer cells with “stemness” properties that favor successful colonization in
distant organs and contribute to chemoresistance. Platelet adhesion and activation are required for cancer cell
colonization at the distal sites. We found that silencing Hsp47 in metastatic breast cancer cells significantly
reduced platelet adhesion. These results suggest that Hsp47 promotes TNBC metastasis/relapse by inducing
EMT and platelet recruitment. In Aim 1, we will investigate the molecular mechanism by which Hsp47 regulates
EMT and stemness properties. In Aim 2, we will determine the cellular mechanism by which Hsp47 promotes
colonization of breast cancer cells at the secondary organs. In Aim 3, we will define the roles of Hsp47 in
promoting cancer metastasis and chemoresistance in TNBC. This investigation will change the current
concept of ECM microenvironment in cancer metastasis by revealing new roles of cancer cell-derived collagen
in inducing cancer cell-platelet interaction and metastasis. Characterization of Hsp47 as a hub of
collagen/DDR2 signaling will identify a novel pathway to inhibit TNBC progression and chemoresistance.

## Key facts

- **NIH application ID:** 10114980
- **Project number:** 5R01CA207772-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ren Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,269
- **Award type:** 5
- **Project period:** 2017-03-03 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114980

## Citation

> US National Institutes of Health, RePORTER application 10114980, Roles of Hsp47 in breast cancer progression (5R01CA207772-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10114980. Licensed CC0.

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