Research field: Malignant progression of Cancer
Cell-cell adhesion is a crucial process that underlies cell differentiation, tissue development, and tissue homeostasis. However, in epithelial neoplasia, the acquisition of motile or invasive properties by cancerous cells leads to poor prognosis. Epithelial-mesenchymal transition (EMT) is a natural phenomenon involved in cellular movement and plays a vital role in morphogenesis. In the context of cancer progression, EMT can be abnormally induced through various signaling pathways. Transcription factors, ZEB2, and ZEB1, significantly influence the phenotypic conversion during EMT. These factors reprogram the epithelium, imparting new biochemical instructions associated with malignant behavior in cells. Our research focuses on how these EMT-inducing transcription factors enable benign cancer cells to acquire the necessary traits for executing the entire invasion-metastasis cascade. We investigate their functional interactors and target genes, which likely increase stemness, initiate tumour formation, activate motility and invasion, and modulate cell death mechanisms. Yet, admidst this pursuit of discovery the development of anti-plasticity therapies emerges. The knowledge gleaned from innovative cancer cell model systems and the blending of functional genomic screens and genomic approaches results in comprehensive insights into the mechanisms underlying epithelial plasticity and its impact on cancer progression and unlocks potential targets for therapeutic intervention.
Areas of Expertise
- Epithelial Mesenchymal Plasticity (EMP) of cancer cells
- Invasion and metastasis of cancer cells
- Transcriptional gene regulation – Reporter assays
- Reverse Genetics: RNAi, CRISPR/CAS9
- Genome-wide expression and epigenetic analysis
Technology Transfer Potential
- Identification of cancer targets in particular novel invasion and metastasis regulators
- Development of plastistatic therapy
Selected publications
- Haerinck, J., Goossens, S. & Berx, G. The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation. Nat Rev Genet 24, 590-609 (2023). Visit ➚
- Vandamme, N. et al. The EMT transcription factor ZEB2 promotes proliferation of primary and metastatic melanoma while suppressing an invasive, mesenchymal-like phenotype. Cancer Res 80, 2983-2995 (2020). Visit ➚
- Slowicka, K. et al. Zeb2 drives invasive and microbiota-dependent colon carcinoma. Nature Cancer 1, 620-634 (2020). Visit ➚
- Scott, C. L. et al. The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2. J Exp Med 213, 897-911 (2016). Visit ➚
- De Craene, B. & Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97-110 (2013). Visit ➚
Bibliography
- Full bibliography Visit ➚