IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells
Triple-negative breast cancer (TNBC) is an aggressive breast tumor subtype that currently lacks targeted treatment options. The role played by the insulin-like growth factor-1 (IGF-1) and its cognate receptor IGF-1R in TNBC has been reported. Nevertheless, the molecular mechanisms by which the IGF-1...
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MDPI AG
2020-04-01
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| author | Damiano Cosimo Rigiracciolo Nijiro Nohata Rosamaria Lappano Francesca Cirillo Marianna Talia Domenica Scordamaglia J. Silvio Gutkind Marcello Maggiolini |
| author_facet | Damiano Cosimo Rigiracciolo Nijiro Nohata Rosamaria Lappano Francesca Cirillo Marianna Talia Domenica Scordamaglia J. Silvio Gutkind Marcello Maggiolini |
| author_sort | Damiano Cosimo Rigiracciolo |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is an aggressive breast tumor subtype that currently lacks targeted treatment options. The role played by the insulin-like growth factor-1 (IGF-1) and its cognate receptor IGF-1R in TNBC has been reported. Nevertheless, the molecular mechanisms by which the IGF-1/IGF-1R system may contribute to TNBC progression still remains to be fully understood. By computational analysis of the vast cancer genomics information in public databases (TCGA and METABRIC), we obtained evidence that high IGF-1 or IGF-1R levels correlate with a worse clinical outcome in TNBC patients. Further bioinformatics analysis revealed that both the focal adhesion and the Hippo pathways are enriched in TNBC harboring an elevated expression of IGF-1 or IGF-1R. Mechanistically, we found that in TNBC cells, the IGF-1/IGF-1R system promotes the activation of the FAK signal transduction pathway, which in turn regulates the nuclear accumulation of YAP (yes-associated protein/yes-related protein) and the expression of its target genes. At the biological level, we found that the IGF-1/IGF-1R-FAK-YAP network cascade triggers the growth potential of TNBC cells, as evaluated in different experimental systems. Overall, our results suggest that the IGF-1/IGF-1R/FAK/YAP axis may contribute to the progression of the aggressive TNBC subtype. |
| first_indexed | 2024-03-10T20:23:34Z |
| format | Article |
| id | doaj.art-c7f30cc8ca3c43d4abeb98b7e11193da |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:23:34Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c7f30cc8ca3c43d4abeb98b7e11193da2023-11-19T22:02:24ZengMDPI AGCells2073-44092020-04-0194101010.3390/cells9041010IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) CellsDamiano Cosimo Rigiracciolo0Nijiro Nohata1Rosamaria Lappano2Francesca Cirillo3Marianna Talia4Domenica Scordamaglia5J. Silvio Gutkind6Marcello Maggiolini7Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyMSD K.K., Tokyo 102-8667, JapanDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USADepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyTriple-negative breast cancer (TNBC) is an aggressive breast tumor subtype that currently lacks targeted treatment options. The role played by the insulin-like growth factor-1 (IGF-1) and its cognate receptor IGF-1R in TNBC has been reported. Nevertheless, the molecular mechanisms by which the IGF-1/IGF-1R system may contribute to TNBC progression still remains to be fully understood. By computational analysis of the vast cancer genomics information in public databases (TCGA and METABRIC), we obtained evidence that high IGF-1 or IGF-1R levels correlate with a worse clinical outcome in TNBC patients. Further bioinformatics analysis revealed that both the focal adhesion and the Hippo pathways are enriched in TNBC harboring an elevated expression of IGF-1 or IGF-1R. Mechanistically, we found that in TNBC cells, the IGF-1/IGF-1R system promotes the activation of the FAK signal transduction pathway, which in turn regulates the nuclear accumulation of YAP (yes-associated protein/yes-related protein) and the expression of its target genes. At the biological level, we found that the IGF-1/IGF-1R-FAK-YAP network cascade triggers the growth potential of TNBC cells, as evaluated in different experimental systems. Overall, our results suggest that the IGF-1/IGF-1R/FAK/YAP axis may contribute to the progression of the aggressive TNBC subtype.https://www.mdpi.com/2073-4409/9/4/1010TNBCIGF-1IGF-1RFAKYAPOSI-906 |
| spellingShingle | Damiano Cosimo Rigiracciolo Nijiro Nohata Rosamaria Lappano Francesca Cirillo Marianna Talia Domenica Scordamaglia J. Silvio Gutkind Marcello Maggiolini IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells Cells TNBC IGF-1 IGF-1R FAK YAP OSI-906 |
| title | IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells |
| title_full | IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells |
| title_fullStr | IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells |
| title_full_unstemmed | IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells |
| title_short | IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells |
| title_sort | igf 1 igf 1r fak yap transduction signaling prompts growth effects in triple negative breast cancer tnbc cells |
| topic | TNBC IGF-1 IGF-1R FAK YAP OSI-906 |
| url | https://www.mdpi.com/2073-4409/9/4/1010 |
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