University of Oulu

Montoro-García, S., Alburquerque-González, B., Bernabé-García, Á. et al. Novel anti-invasive properties of a Fascin1 inhibitor on colorectal cancer cells. J Mol Med 98, 383–394 (2020). https://doi.org/10.1007/s00109-020-01877-z

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

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Author: Montoro-García, Silvia1; Alburquerque-González, Begoña2; Bernabé-García, Ángel3;
Organizations: 1Cell Culture Lab. Health Faculty, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos, s/n, Guadalupe, 30107, Murcia, Spain
2Pathology and Histology Department. Heatlh Faculty, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos, s/n, Guadalupe, 30107, Murcia, Spain
3Molecular Oncology and TGF-ß Lab, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Carretera Madrid-Cartagena. El Palmar, Murcia, Spain
4Telomerase, Cancer and Aging Group, University Clinical Hospital “Virgen de la Arrixaca”, Biomedical Research Institute of Murcia (IMIB-Arrixaca) Murcia, Murcia, Spain
5Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, Aapistie 5A, FI-90220, Oulu, Finland
6Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
7Eurofins Villapharma Research, Parque Tecnológico de Fuente Álamo. Ctra. El Estrecho-Lobosillo, Km 2,5. Av. Azul E, 30320, Murcia, Spain
8Department of Physical Chemistry and Institute of Biotechnology, University of Granada, Campus Fuentenueva s/n 18071 Granada, Granada, Spain
9Structural Bioinformatics and High Performance Computing (BIO-HPC) Research Group, Universidad Católica de Murcia (UCAM), Guadalupe, Spain
10Institute of Oral and Maxillofacial Disease, University of Helsinki, Helsinki, Finland
11HUSLAB, Department of Pathology, Helsinki University Hospital, Helsinki, Finland
12Clinical Analysis Department, Group of Molecular Pathology and Pharmacogenetics, Biomedical Research Institute from Murcia (IMIB), Hospital Universitario Santa Lucía, c/Mezquita sn, 30202, Cartagena, Spain
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2020061543250
Language: English
Published: Springer Nature, 2020
Publish Date: 2021-01-29
Description:

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.

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Series: Journal of molecular medicine
ISSN: 0946-2716
ISSN-E: 1432-1440
ISSN-L: 0946-2716
Volume: 98
Pages: 383 - 394
DOI: 10.1007/s00109-020-01877-z
OADOI: https://oadoi.org/10.1007/s00109-020-01877-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: This project received grants from Instituto de Salud Carlos III (Spanish Ministry of Health) and FEDER funds (ref: PI12/1232 and PI15/00626), Spanish Ministry of Economy and Competitiveness MINECO (CTQ2017-87974-R), and by the Fundación Séneca del Centro de Coordinación de la Investigación de la Región de Murcia under Projects 18946/JLI/13 and 20646/JLI/18. BAG belongs to the “Programa de Doctorado en Ciencias de la Salud, Universidad Católica de Murcia (UCAM)” and holds a grant of the UCAM. PCR was supported by Finnish Cultural Foundation Grant (2017-2018).
Copyright information: © Springer-Verlag GmbH Germany, part of Springer Nature 2020. This is a post-peer-review, pre-copyedit version of an article published in J Mol Med. The final authenticated version is available online at https://doi.org/10.1007/s00109-020-01877-z.