Oral Presentation 14th International Biennial Conference on Metastasis Research 2012

Overexpression of the GTP-binding protein rab31 induces a switch from an invasive to a proliferative phenotype in breast cancer cells (#25)

Susanne Sölch 1 , Bettina Grimayer 1 , Bastian Seubert 2 , Thomas Kirchner 3 , Sonja Schäfer 1 , Manfred Schmitt 1 , Thomas Luther 3 , Achim Krüger 2 , Matthias Kotzsch 3 , Viktor Magdolen 1
  1. Clinical Research Unit, Klinikum rechts der Isar TUM, Munich, Germany
  2. Experimental Oncology and Therapy Research, Klinikum rechts der Isar TUM, Munich, Germany
  3. Institute of Pathology, University of Technology, Dresden, Germany

Monomeric GTP-binding Rab proteins regulate intracellular vesicle transport. Several Rab proteins, including rab31, have been shown to affect cancer progression and are related with prognosis in various types of cancer including breast cancer. Previously, we found a significant association of high rab31 mRNA expression levels with poor prognosis in node-negative breast cancer patients. In the present study, we aimed at investigating the impact of rab31 overexpression in breast cancer cells on important aspects of tumor progression in vitro and in vivo.

Breast cancer cell transfectants, with different rab31 expression levels, were analyzed in vitro using proliferation, adhesion, and invasion assays. Subsequently, the impact of rab31 overexpression on experimental metastasis in a xenograft tumor model in mice was monitored. Increased rab31 protein levels were associated with enhanced proliferation of breast cancer cells, a reduced adhesion of cells towards extracellular matrix proteins and decreased invasive capacity through MatrigelTM. Overexpression of an inactive rab31-mutant neither stimulated proliferation nor reduced the adhesive capacity of the cells whereas a constitutively active rab31-mutant showed the same phenotype in MDA-MB-231 cells as rab31 overexpressing cells. Finally, in a xenograft mouse model, we observed a significantly impaired metastatic dissemination of rab31 overexpressing MDA-MB-231 cells to the lung. Taken together, our results demonstrate that rab31 overexpression leads to a switch from an invasive to a proliferative phenotype as indicated by an increased cell proliferation, reduced cell adhesion, and decreased cellular invasion in vitro and in vivo.