Genetic attenuation of <scp>ALDH1A1</scp> increases metastatic potential and aggressiveness in colorectal cancer
Colorectal cancer ranks third in global incidence and second in cancer mortality. Patient-derived models are irreplaceable for studying tumor biology. We established a human epithelial cell line from a rectal adenocarcinoma overexpressing cancer stem cell marker ALDH1A1, and we investigated the effect of ALDH1A1 knockout on tumor cell traits. The cell line and its CRISPR-Cas9 ALDH1A1 knockouts were characterized by genomic and cytogenetic methods (CNV, WES, RNAseq, karyotype), in vitro (proliferation, response to chemotherapy, migration, invasion, apoptosis), and in vivo methods. We identified the landscape of somatic mutations and copy number alterations in the original tumor and the derived cell line. Genetic attenuation of ALDH1A1 was characterized by an increase in migratory potential and extensive metastatic ability, accompanied by reduced growth of subcutaneous xenografts and alterations in gene expression associated with inhibited proliferation and promoted invasion and metastasis, ultimately resulting in dysregulation of the Wnt signaling pathway. Increased metastatic potential was also confirmed in HT-29 cells after ALDH1A1 genetic attenuation. CRISPR-Cas9-mediated editing led to functional, cellular, and molecular changes confirming the role of ALDH1A1 in colorectal cancer carcinogenesis.
Authors
- Tomas SZEMES
- Jaroslav Budiš (ORCID: https://orcid.org/0000-0002-8667-6655)
- Sachin Gulati (ORCID: https://orcid.org/0000-0002-5858-6791)
- Daniel Pinďák (ORCID: https://orcid.org/0000-0003-0413-8907)
- Eva Zomborska
- Peter J. Makovicky (ORCID: https://orcid.org/0000-0001-9307-9982)
- Nicolas Blavet (ORCID: https://orcid.org/0000-0003-2199-9119)
- Georgina Kolníková
- Michal Mego (ORCID: https://orcid.org/0000-0002-6511-6827)
- Monika Buríková (ORCID: https://orcid.org/0000-0002-4697-6389)
- Eva Sedláčková (ORCID: https://orcid.org/0000-0002-0089-1611)
- Peter Dubovan (ORCID: https://orcid.org/0000-0002-0853-4045)
- Zuzana Kozovská (ORCID: https://orcid.org/0000-0002-3508-0093)
- Kristina Ploth Pavlov
- Silvia Tyčiaková (ORCID: https://orcid.org/0000-0003-2919-0410)
- Ondrej Pös (ORCID: https://orcid.org/0000-0003-2491-2285)
- Martina Poturnajova (ORCID: https://orcid.org/0000-0002-3174-290X)
- Boris Tichý (ORCID: https://orcid.org/0000-0001-9252-7974)
- Kristína Jakič (ORCID: https://orcid.org/0000-0002-8251-5328)
- Miroslava Matúšková (ORCID: https://orcid.org/0000-0002-0747-9275)
- Matej Hrnciar
- Nikoleta Mojzesova
- Veronika Repaska
- Miroslav Tomas
- Barbora Svitkova
Institutions
- Slovak University of Technology in Bratislava (SK)
- Central European Institute of Technology (CZ)
- Slovak Medical University (SK)
- Slovak Academy of Sciences (SK)
- National Institute of Oncology (HU)
- Biomedical Research Center of the Slovak Academy of Sciences (SK)
- National Cancer Institute (MY)
- Geneton (Slovakia) (SK)
- Comenius University Bratislava (SK)
Publication Details
- Journal
- Molecular Oncology
- Published
- 2026-02-03
- DOI
- https://doi.org/10.1002/1878-0261.70215
- Citations
- 1
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 24.20
Funders
- European Commission
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Agentúra na Podporu Výskumu a Vývoja
- Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
- Central European Institute of Technology