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http://bura.brunel.ac.uk/handle/2438/28701
Title: | IQGAP1 and NWASP promote human cancer cell dissemination and metastasis by regulating β1-integrin via FAK and MRTF/SRF |
Authors: | Cerutti, C Lucotti, S Menendez, ST Reymond, N Garg, R Romero, IA Muschel, R Ridley, AJ |
Keywords: | cancer metastasis;Rho GTPases;endothelial adhesion;β-integrin;signaling;shear stressI;QGAP1;NWASP;cell-cell adhesion |
Issue Date: | 26-Mar-2024 |
Publisher: | Elsevier |
Citation: | Cerutti, C. et al.(2024) 'IQGAP1 and NWASP promote human cancer cell dissemination and metastasis by regulating β1-integrin via FAK and MRTF/SRF', Cell Reports, 43 (4), 113989, pp. 1 - 48. doi: 10.1016/j.celrep.2024.113989. |
Abstract: | Summary: Attachment of circulating tumor cells to the endothelial cells (ECs) lining blood vessels is a critical step in cancer metastatic colonization, which leads to metastatic outgrowth. Breast and prostate cancers are common malignancies in women and men, respectively. Here, we observe that β1-integrin is required for human prostate and breast cancer cell adhesion to ECs under shear-stress conditions in vitro and to lung blood vessel ECs in vivo. We identify IQGAP1 and neural Wiskott-Aldrich syndrome protein (NWASP) as regulators of β1-integrin transcription and protein expression in prostate and breast cancer cells. IQGAP1 and NWASP depletion in cancer cells decreases adhesion to ECs in vitro and retention in the lung vasculature and metastatic lung nodule formation in vivo. Mechanistically, NWASP and IQGAP1 act downstream of Cdc42 to increase β1-integrin expression both via extracellular signal-regulated kinase (ERK)/focal adhesion kinase signaling at the protein level and by myocardin-related transcription factor/serum response factor (SRF) transcriptionally. Our results identify IQGAP1 and NWASP as potential therapeutic targets to reduce early metastatic dissemination. |
Description: | Data and code availability:
* All data are available in the main text or the supplementary materials. Original western blot images are in the supplemental material.
Blot and imaging data reported in this paper will be shared by the lead contact upon request.
* This paper does not report original code.
* Any additional information required to reanalyze the data reported in this paper is available
from the lead contact, Anne Ridley (anne.ridley@bristol.ac.uk). upon request. Supplemental information is available online at: https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00317-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124724003176%3Fshowall%3Dtrue#supplementaryMaterial . |
URI: | https://bura.brunel.ac.uk/handle/2438/28701 |
DOI: | https://doi.org/10.1016/j.celrep.2024.113989 |
ISSN: | 2639-1856 |
Other Identifiers: | ORCiD: Camilla Cerutti https://orcid.org/0000-0001-9426-686X ORCiD: Serena Lucotti https://orcid.org/0000-0003-1318-4761 ORCiD: Sofia T. Menendez https://orcid.org/0000-0003-0745-1384 ORCiD: Ignacio A. Romero https://orcid.org/0000-0002-0322-9180 ORCiD: Ruth Muschel https://orcid.org/0000-0002-5656-5970 ORCiD: Anne J. Ridley https://orcid.org/0000-0001-8186-5708 113989 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | Copyright © 2024 The Authors. Published by Elsevier Inc. User license Creative Commons Attribution (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ . | 18.49 MB | Adobe PDF | View/Open |
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