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

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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.