Berx Unit - Molecular and Cellular Oncology

Research field: Functions of cancer genes crucial for invasion and metastasis

Group leader: Prof. Dr. Geert Berx

Tel:+32 9 33 13 650  -  Fax:+32 9 221 76 73

(Note: Geert Berx' lab is part of the UGent Department of Biomedical Molecular Biology but not a VIB unit)

Research topic

Cell-cell adhesion is essential during cell differentiation, tissue development, and tissue homeostasis. The poor prognosis in epithelial neoplasia is associated with the acquisition of motile or invasive properties by the cancerous cells. Epithelial-mesenchymal transition (EMT) is a natural process of reshaping epithelia for cellular movement and is an essential process during morphogenesis. EMT is also induced through the abnormal activation of different signaling pathways during cancer progression and organ fibrosis. A crucial role in this phenotypic conversion is played by a subset of transcription factors such as Snail, Slug, SIP1/ZEB2 and EF-1/ZEB1. During EMT, these transcription factors can reprogram the epithelium at the molecular level with new biochemical instructions associated with invasive and metastatic cells. One such important gene downregulated by Snail and SIP1/ZEB2 is the invasion tumour suppressor E-cadherin. We focus particularly on how these EMT-inducing transcription factors enable non-invasive cancer cells to acquire features needed to execute the entire invasion-metastasis cascade. We also study new functional interactors and the target genes of these transcription factors, as they probably can activate motility, inhibit apoptosis, enhance invasion, and dismantle the local basement membrane. For our studies we use in vitro cell systems and in vivo mouse models, and in that way we combine functional genomic screens with genomic approaches.

Area of expertise

  • Invasion and metastasis of cancer cells
  • Genome-wide expression analysis
  • Transcriptional gene regulation
  • Reverse Genetics: RNAi knock-down
  • Conditional gene expression

Technology transfer potential

  • Identification of cancer targets in particular novel invasion and metastasis regulators

Analysis of DMBA/TPA induced tumors in WT mice (left)
and K14 Snail transgenic mice (right) illustrating
the invasive behavior of Snail-expressing tumor cells

Selected publications

  1. van Helden et al., Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection.
    Journal of Experimental Medicine, 2015 (in press).
  2. De Craene, B et al. Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential.
    Cell Death and Differentiation, 21, 310-20, 2014.
  3. De Craene, B et al. Regulatory networks defining EMT during cancer initiation and progression.
    Nature Reviews Cancer, 13, 97-110, 2013.
  4. Vandewalle et al. SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions.
    Nucleic Acids Res 33, 6566-6578, 2005.
  5. Denecker et al., Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression.
    Cell death and differentiation , 21, 1250-1261, 2014.
  6. Comijn, J  et al., The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.
    Mol Cell 7, 1267-1278, 2001.

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