MTA1 drives malignant progression and bone metastasis in prostate cancer
Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis‐associated protein 1 (MTA1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown. Here, we report the role of MTA1 in p...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-09-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12360 |
| _version_ | 1818301733792645120 |
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| author | Avinash Kumar Swati Dhar Gisella Campanelli Nasir A. Butt Jason M. Schallheim Christian R. Gomez Anait S. Levenson |
| author_facet | Avinash Kumar Swati Dhar Gisella Campanelli Nasir A. Butt Jason M. Schallheim Christian R. Gomez Anait S. Levenson |
| author_sort | Avinash Kumar |
| collection | DOAJ |
| description | Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis‐associated protein 1 (MTA1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown. Here, we report the role of MTA1 in prostate cancer progression and bone metastasis in vitro and in vivo. We found that MTA1 silencing diminished formation of bone metastases and impaired tumor growth in intracardiac and subcutaneous prostate cancer xenografts, respectively. This was attributed to reduced colony formation, invasion, and migration capabilities of MTA1 knockdown cells. Mechanistic studies revealed that MTA1 silencing led to a significant decrease in the expression of cathepsin B (CTSB), a cysteine protease critical for bone metastasis, with an expected increase in the levels of E‐cadherin in both cells and xenograft tumors. Moreover, meta‐analysis of clinical samples indicated a positive correlation between MTA1 and CTSB. Together, these results demonstrate the critical role of MTA1 as an upstream regulator of CTSB‐mediated events associated with cell invasiveness and raise the possibility that targeting MTA1/CTSB signaling in the tumor may prevent the development of bone metastasis in prostate cancer. |
| first_indexed | 2024-12-13T05:27:42Z |
| format | Article |
| id | doaj.art-66cddcedde5440789afeb116545388c6 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-13T05:27:42Z |
| publishDate | 2018-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-66cddcedde5440789afeb116545388c62022-12-21T23:58:09ZengWileyMolecular Oncology1574-78911878-02612018-09-011291596160710.1002/1878-0261.12360MTA1 drives malignant progression and bone metastasis in prostate cancerAvinash Kumar0Swati Dhar1Gisella Campanelli2Nasir A. Butt3Jason M. Schallheim4Christian R. Gomez5Anait S. Levenson6Arnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University Brooklyn NY USACancer Institute University of Mississippi Medical Center Jackson MS USAArnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University Brooklyn NY USACancer Institute University of Mississippi Medical Center Jackson MS USADepartment of Pathology University of Mississippi Medical Center Jackson MS USACancer Institute University of Mississippi Medical Center Jackson MS USAArnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University Brooklyn NY USAProstate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis‐associated protein 1 (MTA1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown. Here, we report the role of MTA1 in prostate cancer progression and bone metastasis in vitro and in vivo. We found that MTA1 silencing diminished formation of bone metastases and impaired tumor growth in intracardiac and subcutaneous prostate cancer xenografts, respectively. This was attributed to reduced colony formation, invasion, and migration capabilities of MTA1 knockdown cells. Mechanistic studies revealed that MTA1 silencing led to a significant decrease in the expression of cathepsin B (CTSB), a cysteine protease critical for bone metastasis, with an expected increase in the levels of E‐cadherin in both cells and xenograft tumors. Moreover, meta‐analysis of clinical samples indicated a positive correlation between MTA1 and CTSB. Together, these results demonstrate the critical role of MTA1 as an upstream regulator of CTSB‐mediated events associated with cell invasiveness and raise the possibility that targeting MTA1/CTSB signaling in the tumor may prevent the development of bone metastasis in prostate cancer.https://doi.org/10.1002/1878-0261.12360bone metastasiscathepsin Bintracardiac xenograftsluciferase imagingMTA1prostate cancer |
| spellingShingle | Avinash Kumar Swati Dhar Gisella Campanelli Nasir A. Butt Jason M. Schallheim Christian R. Gomez Anait S. Levenson MTA1 drives malignant progression and bone metastasis in prostate cancer Molecular Oncology bone metastasis cathepsin B intracardiac xenografts luciferase imaging MTA1 prostate cancer |
| title | MTA1 drives malignant progression and bone metastasis in prostate cancer |
| title_full | MTA1 drives malignant progression and bone metastasis in prostate cancer |
| title_fullStr | MTA1 drives malignant progression and bone metastasis in prostate cancer |
| title_full_unstemmed | MTA1 drives malignant progression and bone metastasis in prostate cancer |
| title_short | MTA1 drives malignant progression and bone metastasis in prostate cancer |
| title_sort | mta1 drives malignant progression and bone metastasis in prostate cancer |
| topic | bone metastasis cathepsin B intracardiac xenografts luciferase imaging MTA1 prostate cancer |
| url | https://doi.org/10.1002/1878-0261.12360 |
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