Novel anti-invasive properties of a Fascin1 inhibitor on colorectal cancer cells

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Montoro-Garcia , S , Alburquerque-Gonzalez , B , Bernabe-Garcia , A , Bernabe-Garcia , M , Rodrigues , P C , den-Haan , H , Luque , I , Jose Nicolas , F , Perez-Sanchez , H , Luisa Cayuela , M , Salo , T & Conesa-Zamora , P 2020 , ' Novel anti-invasive properties of a Fascin1 inhibitor on colorectal cancer cells ' , Journal of Molecular Medicine , vol. 98 , no. 3 , pp. 383-394 . https://doi.org/10.1007/s00109-020-01877-z

Title: Novel anti-invasive properties of a Fascin1 inhibitor on colorectal cancer cells
Author: Montoro-Garcia, Silvia; Alburquerque-Gonzalez, Begona; Bernabe-Garcia, Angel; Bernabe-Garcia, Manuel; Rodrigues, Priscila Campioni; den-Haan, Helena; Luque, Irene; Jose Nicolas, Francisco; Perez-Sanchez, Horacio; Luisa Cayuela, Maria; Salo, Tuula; Conesa-Zamora, Pablo
Contributor: University of Helsinki, HUSLAB
Date: 2020-03
Language: eng
Number of pages: 12
Belongs to series: Journal of Molecular Medicine
ISSN: 0946-2716
URI: http://hdl.handle.net/10138/325423
Abstract: Tumor invasion and metastasis involve processes in which actin cytoskeleton rearrangement induced by Fascin1 plays a crucial role. Indeed, Fascin1 has been found overexpressed in tumors with worse prognosis. Migrastatin and its analogues target Fascin1 and inhibit its activity. However, there is need for novel and smaller Fascin1 inhibitors. The aim of this study was to assess the effect of compound G2 in colorectal cancer cell lines and compare it to migrastatin in in vitro and in vivo assays. Molecular modeling, actin-bundling, cell viability, inmunofluorescence, migration, and invasion assays were carried out in order to test anti-migratory and anti-invasive properties of compound G2. In addition, the in vivo effect of compound G2 was evaluated in a zebrafish model of invasion. HCT-116 cells exhibited the highest Fascin1 expression from eight tested colorectal cancer cell lines. Compound G2 showed important inhibitory effects on actin bundling, filopodia formation, migration, and invasion in different cell lines. Moreover, compound G2 treatment resulted in significant reduction of invasion of DLD-1 overexpressing Fascin1 and HCT-116 in zebrafish larvae xenografts; this effect being less evident in Fascin1 known-down HCT-116 cells. This study proves, for the first time, the in vitro and in vivo anti-tumoral activity of compound G2 on colorectal cancer cells and guides to design improved compound G2-based Fascin1 inhibitors. Key messages center dot Fascin is crucial for tumor invasion and metastasis and is overexpressed in bad prognostic tumors. center dot Several adverse tumors overexpress Fascin1 and lack targeted therapy. center dot Anti-fascin G2 is for the first time evaluated in colorectal carcinoma and compared with migrastatin. center dot Filopodia formation, migration activity, and invasion in vitro and in vivo assays were performed. center dot G2 blocks actin structures, migration, and invasion of colorectal cancer cells as fascin-dependent.
Subject: Fascin1
Migrastatin
Invasion
Migration
Zebrafish xenograft
Colorectal cancer
BASAL-LIKE PHENOTYPE
BREAST-CANCER
EXPRESSION
PROGRESSION
MIGRATION
ADENOCARCINOMA
ASSOCIATION
BIOMARKERS
MUTATIONS
PROTEINS
1184 Genetics, developmental biology, physiology
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