Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome
Integrins are cell-extracellular matrix adhesion molecules whose expression level undergoes quantitative changes upon neoplastic transformation and are considered functionally related to the development of cancer metastasis. We analyzed the largest mRNA-seq dataset available to determine the express...
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/2937 |
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| author | Lorenza Mautone Carlo Ferravante Anna Tortora Roberta Tarallo Giorgio Giurato Alessandro Weisz Mario Vitale |
| author_facet | Lorenza Mautone Carlo Ferravante Anna Tortora Roberta Tarallo Giorgio Giurato Alessandro Weisz Mario Vitale |
| author_sort | Lorenza Mautone |
| collection | DOAJ |
| description | Integrins are cell-extracellular matrix adhesion molecules whose expression level undergoes quantitative changes upon neoplastic transformation and are considered functionally related to the development of cancer metastasis. We analyzed the largest mRNA-seq dataset available to determine the expression pattern of integrin family subunits in papillary thyroid carcinomas (PTC). ITGA2, 3, 6, V, and ITGB1 integrin subunits were overexpressed in PTC compared to normal thyroid tissue. The PTC histology variants “classical” and “tall cell” displayed a similar integrin expression profile with a higher level of ITGA3, ITGAV, and ITGB1, which differed from that of the “follicular” variant. Interestingly, compared to RAS mutations, BRAFV600E mutation was associated with a significantly higher expression of integrins. Some integrin subunits were associated with advanced disease stage, lymph node metastasis, extrathyroidal extension, and high-risk groups. Among them, ITGA3 expression displayed the highest correlation with advanced disease and was associated with a negative prognosis. In vitro scratch assay and Matrigel invasion assay in two different PTC cell lines confirmed α3β1 role in cell motility and invasion, supporting its involvement during tumor progression. These results demonstrate the existence of a PTC-specific integrin expression signature correlated to histopathology, specific driver gene mutations, and aggressiveness of the disease. |
| first_indexed | 2024-03-10T10:29:41Z |
| format | Article |
| id | doaj.art-d959686a20a748ce96b9cb259fc28262 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:29:41Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d959686a20a748ce96b9cb259fc282622023-11-21T23:46:41ZengMDPI AGCancers2072-66942021-06-011312293710.3390/cancers13122937Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst OutcomeLorenza Mautone0Carlo Ferravante1Anna Tortora2Roberta Tarallo3Giorgio Giurato4Alessandro Weisz5Mario Vitale6Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyIntegrins are cell-extracellular matrix adhesion molecules whose expression level undergoes quantitative changes upon neoplastic transformation and are considered functionally related to the development of cancer metastasis. We analyzed the largest mRNA-seq dataset available to determine the expression pattern of integrin family subunits in papillary thyroid carcinomas (PTC). ITGA2, 3, 6, V, and ITGB1 integrin subunits were overexpressed in PTC compared to normal thyroid tissue. The PTC histology variants “classical” and “tall cell” displayed a similar integrin expression profile with a higher level of ITGA3, ITGAV, and ITGB1, which differed from that of the “follicular” variant. Interestingly, compared to RAS mutations, BRAFV600E mutation was associated with a significantly higher expression of integrins. Some integrin subunits were associated with advanced disease stage, lymph node metastasis, extrathyroidal extension, and high-risk groups. Among them, ITGA3 expression displayed the highest correlation with advanced disease and was associated with a negative prognosis. In vitro scratch assay and Matrigel invasion assay in two different PTC cell lines confirmed α3β1 role in cell motility and invasion, supporting its involvement during tumor progression. These results demonstrate the existence of a PTC-specific integrin expression signature correlated to histopathology, specific driver gene mutations, and aggressiveness of the disease.https://www.mdpi.com/2072-6694/13/12/2937integrinsthyroid cancerBRAF mutation |
| spellingShingle | Lorenza Mautone Carlo Ferravante Anna Tortora Roberta Tarallo Giorgio Giurato Alessandro Weisz Mario Vitale Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome Cancers integrins thyroid cancer BRAF mutation |
| title | Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome |
| title_full | Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome |
| title_fullStr | Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome |
| title_full_unstemmed | Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome |
| title_short | Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome |
| title_sort | higher integrin alpha 3 beta1 expression in papillary thyroid cancer is associated with worst outcome |
| topic | integrins thyroid cancer BRAF mutation |
| url | https://www.mdpi.com/2072-6694/13/12/2937 |
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