Using the Drosophila fly intestine to investigate Wnt targets in vivo

结直肠癌是第三大常见癌症，也是癌症死亡的第二大常见原因。Apc（Adenomatous Polyposis Coli）基因在近80%的癌症中突变，但在其他癌症中很少突变。此外，Apc突变似乎发生在结直肠癌的最早阶段。因此，了解Apc突变对结肠正常细胞的影响至关重要。这已经被证明在取自人类和小鼠的细胞中进行研究特别困难，因为正常的结肠细胞在实验室的塑料培养皿中不能很好地存活。此外，从患者身上提取的结直肠癌细胞已经失去了Apc基因，因此很难阐明Apc在正常细胞中阻止癌症的作用。因此，已经在小鼠中进行了许多研究，其中通过遗传技术在成年肠/结肠中去除Apc基因，然后监测发生的变化。在这项提议中，我们的目标是评估是否从果蝇肠道中去除APC将是一个同样好的模型，用于研究所发生的变化。具体来说，我们对称为Wnt的信号通路感兴趣，该信号通路在Apc丢失后上升，并且在苍蝇，小鼠和人类之间非常相似。因此，我们的目标是敲除在Apc丢失后上升的蛋白质，看看它们是否可以阻止癌症。如果我们能够验证苍蝇作为这些研究的测试系统，这将大大减少我们需要执行的小鼠实验的数量。此外，这项工作可能为治疗结直肠癌提供新的治疗靶点，

Colorectal Cancer is the third most common cancer and the second most common cause of cancer death. The Apc (Adenomatous Polyposis Coli) gene is mutated in nearly 80% of cancers but rarely in other cancers. Moreover Apc mutation appears to occur at the very earliest stages of colorectal cancer. Therefore it is vital for us to understand what the impact Apc mutation has upon normal cells from the colon. This has proved particularly difficult to study in cells taken from humans and mice as normal colon cells do not surivive well in the laboratory on plastic dishes. Also colorectal cancer cells taken from patients have already lost the Apc gene so making it difficult to elucidate what Apc does in normal cells to stop cancer. Therefore numerous studies have been performed in mice where the Apc gene is removed by genetic technology in the adult intestine/colon and then the changes that occur are monitored. In this proposal, we aim to assess whether removing Apc from the Drosophila fruitfly intestine would be an equally good model for studying the changes that occur. Specifically we are interested in the signalling pathway called Wnt which goes up following Apc loss and is very similar between flies, mice and humans. Thus our aim is to knockdown the proteins that go up following Apc loss and see if they can stop cancer. If we can validate the fly as test system for these studies, this will reduce the number of mouse experiments dramatically we need to perform. Moreover, this work may provide novel therapeutic targets for the treatment of colorectal cancer,