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

癌细胞侵袭抑制因子（SCAI）是脊椎动物中一种特征性不强但高度保守的蛋白质。我们的工作最初表明，SCAI通过抑制MAL来控制人类癌细胞的侵袭特性，MAL也称为MTRF-A（心肌蛋白相关转录因子A），是血清反应因子（SRF）的共激活因子。SCAI表达在大量不同实体的人类癌症标本中减少，表明SCAI可能具有作为肿瘤抑制剂的潜在功能。为了现在分析SCAI的体内功能，我们在之前的资助期间产生并获得了SCAI缺陷小鼠。到目前为止，这些动物是可行的，这表明SCAI对胚胎发育不是必需的。因此，我们计划（i）研究SCAI缺陷小鼠的自发肿瘤发展;（ii）使用已建立的低转移发生率转基因肿瘤小鼠模型分析SCAI是否影响肿瘤进展;（iii）研究SCAI的基因表达谱，与来自SCAI野生型动物的肿瘤相比较，并在相关细胞培养模型中分析关于细胞侵袭和增殖的靶基因系统使用各自基因产物的过表达和沉默。

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.