PhD Scientific Days 2025

Poster Session II. - E: Pathological and Oncological Sciences

Reactivation of Developmental Pathways is Associated with High Migration Potential in Mesothelioma Cells

Name of the presenter

Dobos Nikolett Kitti

Institute/workplace of the presenter

Pázmány Péter Catholic University, Faculty of Information Technology and Bionics

Authors

Nikolett Kitti Dobos¹, Gréta Lilla Bányai¹, Balázs Hegedüs², Tamás Márton Garay^1,3

1: Pázmány Péter Catholic University
2: University of Duisburg-Essen
3: Semmelweis University

Text of the abstract

Malignant mesothelioma (MM) is an aggressive cancer arising in mesothelial cells lining body cavities. Despite being a rare disease, the number of affected individuals is on the rise, with very few therapeutic options available. The migration of tumor cells plays a crucial role in the progression of the disease, namely invasion and metastasis. Due to the anatomical conditions, the tumor grows in a preformed two-dimensional space, making single-cell tracking a particularly relevant method for modeling migratory behavior.
The aim of the study was to identify gene expression signatures underlying MM cell migration potential.
Migration speed (Total Traveled Distance, TTD) of 14 MM cell lines over 24 hours was quantified using single-cell tracking (CellTracker) and the cell lines were classified into "slow" and "fast" cohorts. RNA sequencing was performed (Illumina MiSeq) followed by differential gene expression (DEG) analysis between cohorts (R/Bioconductor; p<0.05, |logFC|>1). Functional enrichment analysis utilized Gene Ontology and KEGG pathways.
DEG analysis identified 111 genes, of which the most were upregulated in the “slow” cohort, distinguishing fast vs. slow migrating cells. Functional enrichment revealed these genes are predominantly associated with developmental processes (25.2%), signal transduction (20.7%), and cell adhesion, ECM interaction, and cytoskeleton dynamics (10.8%). Other significant categories included metabolism/transport/protein modification (8.1%), non-coding RNAs (7.2%), immune interaction (3.6%), and apoptosis regulation (0.9%). A subset of genes (23.4%) remains functionally uncharacterized or irrelevant.
To conclude, the genes underlying mesothelioma cell migration may generally be of developmental origin. Re-activating these developmental programs is a common strategy used by cancer cells to gain migratory and invasive capabilities. This supports the idea that the up- or downregulation of these genes may affect mesothelioma cell migrational behavior.
In conclusion, MM cell migration speed is associated with distinct gene expression profiles, prominently featuring the reactivation of developmental pathways alongside core signaling and motility programs. This suggests that targeting these aberrantly expressed genes could represent novel strategies to inhibit MM progression and metastasis.