The Department of Biomedicine

BBB seminar: Anna M. Aragay

The cadherin-catenin adhesion system in signalling and cancer

Anna M. Aragay
Department of Biomedicine, University of Bergen

The loosening of intracellular adhesiveness at invasive carcinomas is due to functional disturbance of E-cadherin-mediated cell-cell contacts. Several mechanisms for inactivation of cadherin-mediated cell-cell adhesion have been proposed in human cancer. The majority of epithelial tumours show reduced E-cadherin expression in a heterologous manner and a correlation between reduced E-cadherin expression, loss of tumour differentiation and increased invasiveness has been found. This is consistent with the hypothesis that inhibition of E-cadherin function enhances the release of cancer cells from the primary site.

The distal portion of the cadherin cytoplasmic tail binds to different proteins, which in turn link the adhesive complex to the actin cytoskeleton. One candidate regulator of adhesion that binds to the cytoplasmic tail of cadherins is the catenin p120. Our group has recently discovered a link between the catenin p120 and a protein involved in signalling through cell surface receptors (Krakstad et al., Proc Natl Acad Sci USA. 2004, 101:10314-9). This protein belongs to the family of heterotrimeric G proteins, G12. The finding has opened a new avenue in the field of cell adhesion since it postulates a model of how signalling proteins can affect cadherin-cadherin interaction between cells.


Anna Aragay received a Ph.D. Degree in Biochemistry and Molecular Biology in 1989 from the Universitat Autonoma de Barcelona, Spain, and since then has been working in several research institutions, mainly outside of Spain. Her research interests are in the general area of signalling mechanisms involving G-protein receptors and cell adhesion.

During her Ph.D. she studied the processes leading to the reconstitution of nucleosomes on newly replicated fibres of DNA. In 1990 she moved as a postdoctoral fellow to the California Institute of Technology, where she spent the following six years in the laboratory of Prof. Melvin Simon. Here she was involved in several projects concerned with dissecting G-protein receptor signalling pathways. She developed methodologies to microinject antibodies directly into cultured cells (with Prof. James Feramisco, UCSD) and PCR methods to clone and characterise families of G-proteins in cellular or organism samples (with Dr. Thomas Wilkie, now at the Southwestern Medical School). Some of these collaborations are actively maintained within her group in Bergen. She also spent two years as a senior scientist at the Centro de Biologia Molecular in Madrid, where she worked in collaboration with Profs. Federico Mayor and C. Martinez-A. Together they investigated the role of protein kinases and phosphatases involved in the modulation of G-protein signals, mainly effected through GRK enzymes.

In 2000 Anna Aragay moved to Norway, accepting the position as Associate Professor at the Department of Anatomy and Cell Biology, University of Bergen. She focuses her attention on studying these signalling processes and their implication in cell adhesion and metastasis. She is also head of the National Molecular Imaging Center (MIC).

Selected publication:
Krakstad BF, Ardawatia VV, Aragay AM. A role for Galpha12/Galpha13 in p120ctn regulation. Proc Natl Acad Sci USA. 2004; 101:10314-9.