Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tum
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(2020) 18:144
RESEARCH
Open Access
Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation Maria Al Haddad1†, Rayane El-Rif1†, Samer Hanna2, Leila Jaafar1, Rayanne Dennaoui1, Sandra Abdellatef1, Veronika Miskolci3, Dianne Cox4,5, Louis Hodgson4,5 and Mirvat El-Sibai1*
Abstract Background: Lung cancer is the second most commonly occurring cancer. The ability to metastasize and spread to distant locations renders the tumor more aggressive. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in the regulation of the actin cytoskeleton and in cancer cell migration and metastasis. In this study we investigated the role of the RhoA/Cdc42 GAP, StarD13, a previously described tumor suppressor, in malignancy, migration and invasion of the lung cancer cells A549. Methods: We knocked down StarD13 expression in A549 lung cancer cells and tested the effect on cell migration and invadopodia formation using time lapse imaging and invasion assays. We also performed rescue experiments to determine the signaling pathways downstream of StarD13 and transfected the cells with FRET biosensors for RhoGTPases to identify the proteins involved in invadopodia formation. (Continued on next page)
* Correspondence: [email protected] † Maria Al-Haddad and Rayane El-Rif contributed equally to this work. 1 Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box: 13-5053. Chouran, Beirut 1102 2801, Lebanon Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Al Haddad et al. Cell Communication and Signaling
(2020) 18:144
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Results: We observed a decrease in the level of expression of StarD13 in lung tumor tissues compared to normal lung tissues through immunohistochemistry. StarD13 also showed a lower expression in th
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