Arl13b regulates breast cancer cell migration and invasion by controlling integrin-mediated signaling

Cristina Casalou, Alexandra Faustino, Fernanda Silva, Inês C. Ferreira, Daniela Vaqueirinho, Andreia Ferreira, Pedro Castanheira, Teresa Barona, José S. Ramalho, Jacinta Serpa, Ana Félix, Duarte C. Barral

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Abstract

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.

Original languageEnglish
Article number1461
JournalCancers
Volume11
Issue number10
DOIs
Publication statusPublished - 1 Oct 2019

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Integrins
Cell Movement
Breast Neoplasms
Neoplasms
Focal Adhesions
Neoplasm Metastasis
Cell Line
Mortality
Actin Cytoskeleton
Oncogenes
Cell Adhesion
In Vitro Techniques

Keywords

  • Actin cytoskeleton
  • Arl proteins
  • Cancer progression
  • Cell-extracellular matrix adhesion
  • Integrins

Cite this

@article{d437299612734d559f1aa84e2c3fdf59,
title = "Arl13b regulates breast cancer cell migration and invasion by controlling integrin-mediated signaling",
abstract = "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.",
keywords = "Actin cytoskeleton, Arl proteins, Cancer progression, Cell-extracellular matrix adhesion, Integrins",
author = "Cristina Casalou and Alexandra Faustino and Fernanda Silva and Ferreira, {In{\^e}s C.} and Daniela Vaqueirinho and Andreia Ferreira and Pedro Castanheira and Teresa Barona and Ramalho, {Jos{\'e} S.} and Jacinta Serpa and Ana F{\'e}lix and Barral, {Duarte C.}",
note = "This work was supported by PhD fellowships from Funda{\cc}{\~a}o para a Ci{\^e}ncia e a Tecnologia(FCT) to A. Faustino, A. Ferreira and P.C. (PD/BD/105898/2014, PD/BD/135506/2018 and PD/BD/128339/2017, respectively), a post-doctoral fellowship from FCT to C.C. (SFRH/BPD/78561/2011), the FCT Investigator Program to D.C.B. (IF/00501/2014/CP1252/CT0001), and grants from FCT (PTDC/BIM-MEC/4905/2014) and iNOVA4Health - UID/Multi/04462/2013, a program financially supported by FCT/ Minist{\'e}rio da Educa{\cc}{\~a}o e Ci{\^e}ncia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.",
year = "2019",
month = "10",
day = "1",
doi = "10.3390/cancers11101461",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute",
number = "10",

}

Arl13b regulates breast cancer cell migration and invasion by controlling integrin-mediated signaling. / Casalou, Cristina; Faustino, Alexandra; Silva, Fernanda; Ferreira, Inês C.; Vaqueirinho, Daniela; Ferreira, Andreia; Castanheira, Pedro; Barona, Teresa; Ramalho, José S.; Serpa, Jacinta; Félix, Ana; Barral, Duarte C.

In: Cancers, Vol. 11, No. 10, 1461, 01.10.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Arl13b regulates breast cancer cell migration and invasion by controlling integrin-mediated signaling

AU - Casalou, Cristina

AU - Faustino, Alexandra

AU - Silva, Fernanda

AU - Ferreira, Inês C.

AU - Vaqueirinho, Daniela

AU - Ferreira, Andreia

AU - Castanheira, Pedro

AU - Barona, Teresa

AU - Ramalho, José S.

AU - Serpa, Jacinta

AU - Félix, Ana

AU - Barral, Duarte C.

N1 - This work was supported by PhD fellowships from Fundação para a Ciência e a Tecnologia(FCT) to A. Faustino, A. Ferreira and P.C. (PD/BD/105898/2014, PD/BD/135506/2018 and PD/BD/128339/2017, respectively), a post-doctoral fellowship from FCT to C.C. (SFRH/BPD/78561/2011), the FCT Investigator Program to D.C.B. (IF/00501/2014/CP1252/CT0001), and grants from FCT (PTDC/BIM-MEC/4905/2014) and iNOVA4Health - UID/Multi/04462/2013, a program financially supported by FCT/ Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - Actin cytoskeleton

KW - Arl proteins

KW - Cancer progression

KW - Cell-extracellular matrix adhesion

KW - Integrins

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U2 - 10.3390/cancers11101461

DO - 10.3390/cancers11101461

M3 - Article

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 10

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ER -