Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissue
Abstract Fibrosis is an important feature of adipose tissue in obese individuals; nevertheless, roles of obesity-associated extracellular matrix (ECM) deposition in breast cancer progression largely remain elusive. Here, we show that expression of Hsp47, a chaperone protein involving collagen secret...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Breast Cancer Research |
| Online Access: | https://doi.org/10.1186/s13058-025-02076-9 |
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| author | Gaofeng Xiong Daheng He Dana Napier Jing Chen Haizhu Shi Chun Li Paula J. Hurley Chi Wang Haining Zhu Changcheng Zhou Theresa J. Bocklage Ren Xu |
| author_facet | Gaofeng Xiong Daheng He Dana Napier Jing Chen Haizhu Shi Chun Li Paula J. Hurley Chi Wang Haining Zhu Changcheng Zhou Theresa J. Bocklage Ren Xu |
| author_sort | Gaofeng Xiong |
| collection | DOAJ |
| description | Abstract Fibrosis is an important feature of adipose tissue in obese individuals; nevertheless, roles of obesity-associated extracellular matrix (ECM) deposition in breast cancer progression largely remain elusive. Here, we show that expression of Hsp47, a chaperone protein involving collagen secretion, is induced in adipose tissue from obese humans and mice. Adipocyte-specific Hsp47 deletion (Adi-KO) suppresses the high-fat diet (HFD)-induced obesity and mammary tumor progression, accompanied by a reduction in ECM deposition. Matrisome analyses lead to the identification of asporin as a new target of Hsp47 in adipose tissue. Co-immunoprecipitation results confirm that the recruitment of Hsp47 enhances asporin secretion in adipocytes. We further show that knockout of asporin suppresses HFD-induced mammary tumor growth, while exogenous of asporin partially rescues tumor growth in the decellularized mammary gland derived from Hsp47 Adi-KO mice. These results indicate that asporin at least partially mediates Hsp47 function in HFD-associated tumor progression. Digital spatial profiling (DSP) analyses show that Hsp47 depletion significantly increases the accumulation of CD8 T cells in tumor and tumor-associated adipose tissues. These results implicate that Hsp47, along with-it mediated ECM deposition, suppresses the anti-tumor immunity under HFD conditions. These findings reveal Hsp47 as a novel target for mitigating obesity-associated breast cancer progression. |
| format | Article |
| id | doaj-art-1cb04e6863294e0db2dbe76a1681326d |
| institution | DOAJ |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-1cb04e6863294e0db2dbe76a1681326d2025-08-20T03:06:31ZengBMCBreast Cancer Research1465-542X2025-07-0127111710.1186/s13058-025-02076-9Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissueGaofeng Xiong0Daheng He1Dana Napier2Jing Chen3Haizhu Shi4Chun Li5Paula J. Hurley6Chi Wang7Haining Zhu8Changcheng Zhou9Theresa J. Bocklage10Ren Xu11Markey Cancer Center, University of KentuckyMarkey Cancer Center, University of KentuckyDepartment of Pathology, College of Medicine, University of KentuckyDepartment of Molecular and Cellular Biochemistry, College of Medicine, University of KentuckyMarkey Cancer Center, University of KentuckyMarkey Cancer Center, University of KentuckyDepartment of Medicine, Vanderbilt University Medical CenterMarkey Cancer Center, University of KentuckyDepartment of Molecular and Cellular Biochemistry, College of Medicine, University of KentuckyDivision of Biomedical Sciences, School of Medicine, University of CaliforniaMarkey Cancer Center, University of KentuckyMarkey Cancer Center, University of KentuckyAbstract Fibrosis is an important feature of adipose tissue in obese individuals; nevertheless, roles of obesity-associated extracellular matrix (ECM) deposition in breast cancer progression largely remain elusive. Here, we show that expression of Hsp47, a chaperone protein involving collagen secretion, is induced in adipose tissue from obese humans and mice. Adipocyte-specific Hsp47 deletion (Adi-KO) suppresses the high-fat diet (HFD)-induced obesity and mammary tumor progression, accompanied by a reduction in ECM deposition. Matrisome analyses lead to the identification of asporin as a new target of Hsp47 in adipose tissue. Co-immunoprecipitation results confirm that the recruitment of Hsp47 enhances asporin secretion in adipocytes. We further show that knockout of asporin suppresses HFD-induced mammary tumor growth, while exogenous of asporin partially rescues tumor growth in the decellularized mammary gland derived from Hsp47 Adi-KO mice. These results indicate that asporin at least partially mediates Hsp47 function in HFD-associated tumor progression. Digital spatial profiling (DSP) analyses show that Hsp47 depletion significantly increases the accumulation of CD8 T cells in tumor and tumor-associated adipose tissues. These results implicate that Hsp47, along with-it mediated ECM deposition, suppresses the anti-tumor immunity under HFD conditions. These findings reveal Hsp47 as a novel target for mitigating obesity-associated breast cancer progression.https://doi.org/10.1186/s13058-025-02076-9 |
| spellingShingle | Gaofeng Xiong Daheng He Dana Napier Jing Chen Haizhu Shi Chun Li Paula J. Hurley Chi Wang Haining Zhu Changcheng Zhou Theresa J. Bocklage Ren Xu Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissue Breast Cancer Research |
| title | Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissue |
| title_full | Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissue |
| title_fullStr | Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissue |
| title_full_unstemmed | Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissue |
| title_short | Hsp47 drives obesity-associated breast cancer progression by enhancing asporin deposition in adipose tissue |
| title_sort | hsp47 drives obesity associated breast cancer progression by enhancing asporin deposition in adipose tissue |
| url | https://doi.org/10.1186/s13058-025-02076-9 |
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