Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells
Cancer-associated fibroblasts (CAFs) represent one of the main components in the tumor stroma and play a key role in breast cancer progression. Transforming growth factor-β (TGF-β) has been established to mediate breast cancer metastasis by regulating the epithelial-mesenchymal transition (EMT) and...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-11-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022150 |
| _version_ | 1797635343563882496 |
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| author | Huang Qingyun Wu Longyuan Wang Yi Kong Xinyu Xiao Xinhua Huang Qiyuan Li Miao Zhai Yujia Shi Fuxiu Zhao Ruichen Zhong Junpei Xiong Lixia |
| author_facet | Huang Qingyun Wu Longyuan Wang Yi Kong Xinyu Xiao Xinhua Huang Qiyuan Li Miao Zhai Yujia Shi Fuxiu Zhao Ruichen Zhong Junpei Xiong Lixia |
| author_sort | Huang Qingyun |
| collection | DOAJ |
| description | Cancer-associated fibroblasts (CAFs) represent one of the main components in the tumor stroma and play a key role in breast cancer progression. Transforming growth factor-β (TGF-β) has been established to mediate breast cancer metastasis by regulating the epithelial-mesenchymal transition (EMT) and stemness of cancer cells. Caveolin-1 (CAV-1) is a scaffold protein of caveolae that is related to the proliferation and metabolism of cancer cells. It is now well demonstrated that CAV-1 deficiency in the tumor stroma is positively correlated with distant metastasis, but the mechanism remains unclear. Here, we explore whether CAV-1-deficient fibroblasts play an essential role in the EMT and stemness of breast cancer cells (BCCs) through TGF-β signaling. We establish a specific small interfering RNA (siRNA) to inhibit CAV-1 expression in fibroblasts and coculture them with BCCs to investigate the effect of CAV‑1-deficient fibroblasts and the tumor microenvironment on breast cancer progression. This study refreshingly points out that CAV-1 deficiency in fibroblasts enhances TGF-β1 secretion and then activates the TGF-β1/Smad signaling pathway of BCCs, thus promoting the metastasis and stemness of BCCs. Collectively, our findings indicate an unexpected role of CAV-1 deficiency in fibroblasts and the tumor microenvironment as a permissive factor, which is regulated by the TGF-β1 signaling pathway in BCCs. |
| first_indexed | 2024-03-11T12:20:51Z |
| format | Article |
| id | doaj.art-775497dd84804c198633e290ffd9ba6c |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:20:51Z |
| publishDate | 2022-11-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-775497dd84804c198633e290ffd9ba6c2023-11-07T01:02:24ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-11-01541587159810.3724/abbs.202215020d259ccCaveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cellsHuang Qingyun0Wu Longyuan1Wang Yi2Kong Xinyu3Xiao Xinhua4Huang Qiyuan5Li Miao6Zhai Yujia7Shi Fuxiu8Zhao Ruichen9Zhong Junpei10Xiong Lixia11["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["The First Affiliated Hospital, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China"]["Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China","Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen 361023, China"]Cancer-associated fibroblasts (CAFs) represent one of the main components in the tumor stroma and play a key role in breast cancer progression. Transforming growth factor-β (TGF-β) has been established to mediate breast cancer metastasis by regulating the epithelial-mesenchymal transition (EMT) and stemness of cancer cells. Caveolin-1 (CAV-1) is a scaffold protein of caveolae that is related to the proliferation and metabolism of cancer cells. It is now well demonstrated that CAV-1 deficiency in the tumor stroma is positively correlated with distant metastasis, but the mechanism remains unclear. Here, we explore whether CAV-1-deficient fibroblasts play an essential role in the EMT and stemness of breast cancer cells (BCCs) through TGF-β signaling. We establish a specific small interfering RNA (siRNA) to inhibit CAV-1 expression in fibroblasts and coculture them with BCCs to investigate the effect of CAV‑1-deficient fibroblasts and the tumor microenvironment on breast cancer progression. This study refreshingly points out that CAV-1 deficiency in fibroblasts enhances TGF-β1 secretion and then activates the TGF-β1/Smad signaling pathway of BCCs, thus promoting the metastasis and stemness of BCCs. Collectively, our findings indicate an unexpected role of CAV-1 deficiency in fibroblasts and the tumor microenvironment as a permissive factor, which is regulated by the TGF-β1 signaling pathway in BCCs.https://www.sciengine.com/doi/10.3724/abbs.2022150caveolin 1cancer-associated fibroblastsbreast neoplasmsepithelial-mesenchymal transitiontransforming growth factor-β |
| spellingShingle | Huang Qingyun Wu Longyuan Wang Yi Kong Xinyu Xiao Xinhua Huang Qiyuan Li Miao Zhai Yujia Shi Fuxiu Zhao Ruichen Zhong Junpei Xiong Lixia Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells Acta Biochimica et Biophysica Sinica caveolin 1 cancer-associated fibroblasts breast neoplasms epithelial-mesenchymal transition transforming growth factor-β |
| title | Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells |
| title_full | Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells |
| title_fullStr | Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells |
| title_full_unstemmed | Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells |
| title_short | Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells |
| title_sort | caveolin 1 deficient fibroblasts promote migration invasion and stemness via activating the tgf β smad signaling pathway in breast cancer cells |
| topic | caveolin 1 cancer-associated fibroblasts breast neoplasms epithelial-mesenchymal transition transforming growth factor-β |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022150 |
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