Arl13b regulates breast cancer cell migration and invasion by controlling integrin-mediated signaling
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Casalou, Cristina
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal
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Faustino, Alexandra
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal - ProRegeM—PhD Program in Mechanisms of Disease and Regenerative Medicine, 1169-056 Lisboa, Portugal
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Silva, Fernanda
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal - Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), 1099-023 Lisboa, Portugal
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Ferreira, Inês C.
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal
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Vaqueirinho, Daniela
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal - Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Ferreira, Andreia
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal
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Castanheira, Pedro
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal - ProRegeM—PhD Program in Mechanisms of Disease and Regenerative Medicine, 1169-056 Lisboa, Portugal
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Barona, Teresa
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal
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Ramalho, José S.
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal
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Serpa, Jacinta
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal - Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), 1099-023 Lisboa, Portugal
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Félix, Ana
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal - Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), 1099-023 Lisboa, Portugal
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Barral, Duarte C.
CEDOC, NOVA Medical School| Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-82 Lisboa, Portugal
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Published in:
- Cancers. - 2019, vol. 11, no. 10, p. 1461
English
Breast cancer is the first cause of cancer-related mortality among women worldwide, according to the most recent estimates. This mortality is mainly caused by the tumors’ ability to form metastases. Cancer cell migration and invasion are essential for metastasis and rely on the interplay between actin cytoskeleton remodeling and cell adhesion. Therefore, understanding the mechanisms by which cancer cell invasion is controlled may provide new strategies to impair cancer progression. We investigated the role of the ADP-ribosylation factor (Arf)-like (Arl) protein Arl13b in breast cancer cell migration and invasion in vitro, using breast cancer cell lines and in vivo, using mouse orthotopic models. We show that Arl13b silencing inhibits breast cancer cell migration and invasion in vitro, as well as cancer progression in vivo. We also observed that Arl13b is upregulated in breast cancer cell lines and patient tissue samples. Moreover, we found that Arl13b localizes to focal adhesions (FAs) and interacts with β3- integrin. Upon Arl13b silencing, β3-integrin cell surface levels and FA size are increased and integrin-mediated signaling is inhibited. Therefore, we uncover a role for Arl13b in breast cancer cell migration and invasion and provide a new mechanism for how ARL13B can function as an oncogene, through the modulation of integrin- mediated signaling.
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Medicine
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https://n2t.net/ark:/12658/srd1319139
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