SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin
Abstract Renal Cell Carcinoma (RCC) is the most common form of all renal cancer cases, and well-known for its highly aggressive metastatic behavior. SMOC2 is a recently described non-structural component of the extracellular matrix (ECM) that is highly expressed during tissue remodeling processes wi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05059-2 |
| _version_ | 1828329412017258496 |
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| author | Daniel Feng Peng Gao Nathalie Henley Marion Dubuissez Nan Chen Louis-Philippe Laurin Virginie Royal Vincent Pichette Casimiro Gerarduzzi |
| author_facet | Daniel Feng Peng Gao Nathalie Henley Marion Dubuissez Nan Chen Louis-Philippe Laurin Virginie Royal Vincent Pichette Casimiro Gerarduzzi |
| author_sort | Daniel Feng |
| collection | DOAJ |
| description | Abstract Renal Cell Carcinoma (RCC) is the most common form of all renal cancer cases, and well-known for its highly aggressive metastatic behavior. SMOC2 is a recently described non-structural component of the extracellular matrix (ECM) that is highly expressed during tissue remodeling processes with emerging roles in cancers, yet its role in RCC remains elusive. Using gene expression profiles from patient samples, we identified SMOC2 as being significantly expressed in RCC tissue compared to normal renal tissue, which correlated with shorter RCC patient survival. Specifically, de novo protein synthesis of SMOC2 was shown to be much higher in the tubular epithelial cells of patients with biopsy-proven RCC. More importantly, we provide evidence of SMOC2 triggering kidney epithelial cells into an epithelial-to-mesenchymal transition (EMT), a phenotype known to promote metastasis. We found that SMOC2 induced mesenchymal-like morphology and activities in both RCC and non-RCC kidney epithelial cell lines. Mechanistically, treatment of RCC cell lines ACHN and 786-O with SMOC2 (recombinant and enforced expression) caused a significant increase in EMT-markers, -matrix production, -proliferation, and -migration, which were inhibited by targeting SMOC2 by siRNA. We further characterized SMOC2 activation of EMT to occur through the integrin β3, FAK and paxillin pathway. The proliferation and metastatic potential of SMOC2 overexpressing ACHN and 786-O cell lines were validated in vivo by their significantly higher tumor growth in kidneys and systemic dissemination into other organs when compared to their respective controls. In principle, understanding the impact that SMOC2 has on EMT may lead to more evidence-based treatments and biomarkers for RCC metastasis. |
| first_indexed | 2024-04-13T20:24:47Z |
| format | Article |
| id | doaj.art-8d12d381440e43b88e1a48f80333fd01 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-13T20:24:47Z |
| publishDate | 2022-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-8d12d381440e43b88e1a48f80333fd012022-12-22T02:31:25ZengNature Publishing GroupCell Death and Disease2041-48892022-07-0113711510.1038/s41419-022-05059-2SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma originDaniel Feng0Peng Gao1Nathalie Henley2Marion Dubuissez3Nan Chen4Louis-Philippe Laurin5Virginie Royal6Vincent Pichette7Casimiro Gerarduzzi8Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de MontréalDépartement de Pharmacologie et Physiologie, Faculté de Médecine, Université de MontréalCentre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de MontréalCentre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de MontréalFaculty of Science, University of British ColumbiaCentre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de MontréalCentre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de MontréalDépartement de Pharmacologie et Physiologie, Faculté de Médecine, Université de MontréalDépartement de Pharmacologie et Physiologie, Faculté de Médecine, Université de MontréalAbstract Renal Cell Carcinoma (RCC) is the most common form of all renal cancer cases, and well-known for its highly aggressive metastatic behavior. SMOC2 is a recently described non-structural component of the extracellular matrix (ECM) that is highly expressed during tissue remodeling processes with emerging roles in cancers, yet its role in RCC remains elusive. Using gene expression profiles from patient samples, we identified SMOC2 as being significantly expressed in RCC tissue compared to normal renal tissue, which correlated with shorter RCC patient survival. Specifically, de novo protein synthesis of SMOC2 was shown to be much higher in the tubular epithelial cells of patients with biopsy-proven RCC. More importantly, we provide evidence of SMOC2 triggering kidney epithelial cells into an epithelial-to-mesenchymal transition (EMT), a phenotype known to promote metastasis. We found that SMOC2 induced mesenchymal-like morphology and activities in both RCC and non-RCC kidney epithelial cell lines. Mechanistically, treatment of RCC cell lines ACHN and 786-O with SMOC2 (recombinant and enforced expression) caused a significant increase in EMT-markers, -matrix production, -proliferation, and -migration, which were inhibited by targeting SMOC2 by siRNA. We further characterized SMOC2 activation of EMT to occur through the integrin β3, FAK and paxillin pathway. The proliferation and metastatic potential of SMOC2 overexpressing ACHN and 786-O cell lines were validated in vivo by their significantly higher tumor growth in kidneys and systemic dissemination into other organs when compared to their respective controls. In principle, understanding the impact that SMOC2 has on EMT may lead to more evidence-based treatments and biomarkers for RCC metastasis.https://doi.org/10.1038/s41419-022-05059-2 |
| spellingShingle | Daniel Feng Peng Gao Nathalie Henley Marion Dubuissez Nan Chen Louis-Philippe Laurin Virginie Royal Vincent Pichette Casimiro Gerarduzzi SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin Cell Death and Disease |
| title | SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin |
| title_full | SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin |
| title_fullStr | SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin |
| title_full_unstemmed | SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin |
| title_short | SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin |
| title_sort | smoc2 promotes an epithelial mesenchymal transition and a pro metastatic phenotype in epithelial cells of renal cell carcinoma origin |
| url | https://doi.org/10.1038/s41419-022-05059-2 |
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