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Correction published on 6 December 2020, see Cells 2020, 9(12), 2619.
Article

IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells

1
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
2
MSD K.K., Tokyo 102-8667, Japan
3
Department of Physics, University of Calabria, 87036 Rende, Italy
4
Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(4), 1010; https://doi.org/10.3390/cells9041010
Received: 23 March 2020 / Revised: 9 April 2020 / Accepted: 15 April 2020 / Published: 18 April 2020
(This article belongs to the Collection Compartmentilisation of Cellular Signaling)
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. View Full-Text
Keywords: TNBC; IGF-1; IGF-1R; FAK; YAP; OSI-906; VS-4718; verteporfin TNBC; IGF-1; IGF-1R; FAK; YAP; OSI-906; VS-4718; verteporfin
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MDPI and ACS Style

Rigiracciolo, D.C.; Nohata, N.; Lappano, R.; Cirillo, F.; Talia, M.; Scordamaglia, D.; Gutkind, J.S.; Maggiolini, M. IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells. Cells 2020, 9, 1010. https://doi.org/10.3390/cells9041010

AMA Style

Rigiracciolo DC, Nohata N, Lappano R, Cirillo F, Talia M, Scordamaglia D, Gutkind JS, Maggiolini M. IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells. Cells. 2020; 9(4):1010. https://doi.org/10.3390/cells9041010

Chicago/Turabian Style

Rigiracciolo, Damiano C., Nijiro Nohata, Rosamaria Lappano, Francesca Cirillo, Marianna Talia, Domenica Scordamaglia, J. S. Gutkind, and Marcello Maggiolini. 2020. "IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells" Cells 9, no. 4: 1010. https://doi.org/10.3390/cells9041010

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