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ARTICLE

Metabolism-Targeted Therapy Decreases Proliferation and Migration in CRC-Derived Cells by Modulating Wnt/β-Catenin Signaling Pathway

Samuel Trujano-Camacho1, Verónica García-Castillo1, Sergio Juárez-Méndez2, Héctor Herrera-Orozco1, Eduardo López-Urrutia1, Nadia Jacobo-Herrera3, Eduardo Pérez-Arteaga1, German Calderillo-Ruiz4, David Cantú-de León5, Mauricio Rodríguez-Dorantes6, Jossimar Coronel-Hernández5,*, Carlos Pérez-Plasencia1,*
1 Laboratorio de Genómica Funcional. Unidad de Biomedicina, FES-Iztacala, UNAM, Tlalnepantla, Mexico
2 Laboratorio de Oncología Experimental, Instituto Nacional de Pediatría, Coyoacán, Mexico City, Mexico
3 Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico
4 Unidad Funcional de Gastroenterología, Instituto Nacional de Cancerología, Tlalpan, Mexico City, Mexico
5 Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico City, Mexico
6 Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica, Tlalpan, Mexico City, Mexico
* Corresponding Author: Jossimar Coronel-Hernández. Email: email; Carlos Pérez-Plasencia. Email: email
(This article belongs to the Special Issue: The Identification of Novel Therapeutic Targets and Elucidation of Molecular Mechanisms of Tumorigenesis)

Oncology Research https://doi.org/10.32604/or.2026.073826

Received 26 September 2025; Accepted 01 April 2026; Published online 18 August 2026

Abstract

Background: Colorectal cancer (CRC) is the second most frequent cancer in women and the third most frequent in men. Current therapeutic approaches, including surgery, chemotherapy, and targeted therapy, often exhibit limited specificity and are associated with substantial adverse effects, compromising patient outcomes. Consequently, the medical community constantly pursues more efficient and precisely targeted therapeutic strategies. The aim of the study is to describe the effects of the TT on the Wnt/β-catenin signaling pathway and its role in cell proliferation and migration in an azoxymethane/dextran sulfate sodium (AOM/DSS) mice model and colorectal cancer-derived cell lines. Methods: We treated AOM/DSS mice and HCT116 and SW620 cell lines with the TT, and measured Wnt target genes by quantitative polymerase chain reaction (qPCR) and western blot. β-catenin distribution, activation, transcriptional activity, cell proliferation, and migration were analyzed in HCT116 and SW620 cells. Results: We found that TT significantly decreased the number and size of tumors in AOM/DSS-treated animals. In colorectal cancer cell lines, the TT reduced the expression of AP-1 transcription factor subunit (c-Jun), cellular myelocytomatosis (c-Myc), snail family transcriptional repressor 1 (SNAIL), and vascular endothelial growth factor (VEGF) mRNAs and decreased the activation levels of β-catenin. The most relevant effect of the TT was the cellular delocalization of β-catenin from the nucleus. In addition, it significantly reduced cell proliferation and migration at 24 h in both cell lines. Conclusions: We established that TT decreases proliferation and migration by inducing an impaired localization of β-catenin and deregulation of the transcriptionally active state of this signaling pathway in colorectal cancer-derived cell lines and in a chemically induced mouse model.

Keywords

Wnt/β-catenin; doxorubicin; metformin; oxamate; proliferation; migration; colitis-associated colorectal cancer

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