In vivo relevance of the MAL/SRF suppressor SCAI for tumor progression and metastasis

• Applicant: Professor Dr. Robert Grosse
• Subject Area: Pharmacology
• Term: from 2010 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 157462314

Suppressor of cancer cell invasion (SCAI) is a poorly characterized yet highly conserved protein in vertebrates. Our work initially showed that SCAI controls the invasive properties of human cancer cells through inhibiting MAL, also know as MTRF-A (myocardin-related transcription factor A), a coactivator for the serum response factor (SRF). SCAI expression is diminished in a large array of human cancer specimens of different entities, suggesting that SCAI could have a potential function as a tumor suppressor. In order to now analyze the in vivo function of SCAI we have, during the previous funding period, generated and obtained SCAI-deficient mice. These animals are so far viable, suggesting that SCAI is not essential for embryonic development. We therefore plan to (i) study spontaneous tumor development in SCAI-deficient mice; (ii) analyze whether SCAI impacts on tumor progression using established, transgene tumor mouse models with a low metastasis incidence; (iii) study the gene expression profile of SCAI-deficient tumors in comparison with tumors from SCAI wildtype animals and to analyze target genes with regard to cell invasion and proliferation in a relevant cell culture model system using overexpression and silencing of the respective gene product.

• DFG Programme: Research Grants
• Participating Institution: Max-Planck-Institut für Herz- und Lungenforschung ; W. G. Kerkhoff-Institut ; Abteilung für Pharmakologie; Philipps-Universität Marburg; Fachbereich Medizin; Institut für Molekularbiologie und Tumorforschung (IMT)