Work

OXCT1 knockout suppresses HeLa cell proliferation and invasiveness through adhesion proteins and the PI3K/Akt-Snail pathway

Year: 2026

Type: article

Abstract: While the OXCT1 gene (3-oxoacid CoA-transferase 1, and its gene product SCOT; succinyl-CoA:3-ketoacid CoA transferase) is primarily recognised as the rate-limiting enzyme in ketone body catabolism, accumulating evidence indicates that ketone bodies and ketogenic diets exert complex, context-dependent effects on cancer progression. In this study, we investigated the functional role of OXCT1 in a cervical cancer model using CRISPR/Cas9-mediated gene knockout in HeLa cells. Loss of OXCT1 markedly impaired cell migration and invasion while enhancing intercellular adhesion. These changes were accompanied by downregulation of the β-hydroxybutyrate transporter MCT1, increased expression of adhesion molecules such as E-cadherin, and reduced activation of oncogenic signalling pathways including PI3K/Akt and ERK1/2. Furthermore, OXCT1 -deficient cells exhibited lower levels of epithelial-mesenchymal-transition (EMT)-associated factors, including Snail, together with reduced clonogenic survival under ketogenic conditions. Collectively, these findings indicate that OXCT1 supports HeLa cells, a cervical cancer cell line, proliferation and invasive potential by promoting metabolic flexibility, adhesion remodelling, and pro-invasive signalling. Our data identify OXCT1 as a potential molecular driver of cervical cancer aggressiveness and a putative target for therapeutic intervention.

Source: Scientific Reports

DOI: 10.1038/s41598-026-67087-8

Authors: Kamila Soboska, Maciej Studzian, Marta Biesiekierska, Luciano Pirola, Aneta Balcerczyk

Institutions: University of Łódź, Institute for Medical Biology, Polish Academy of Sciences, Lyon 1 Université, Inserm

Language: English

Topic: Cancer, Lipids, and Metabolism

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690