Developing a Genetic Model to Study Cancer-induced Muscle Wasting
Disciplines
Cancer Biology | Molecular Genetics
Abstract (300 words maximum)
Colorectal tumors are often associated with debilitating skeletal muscle loss, leading to poor cancer patient survival. However, the exact mechanisms driving this effect remain unclear. To identify key genetic factors influencing muscle sensitivity to tumors, our lab uses the Drosophila fruit fly model. In our system, experimental tumors in the fly midgut are induced by overexpressing the mutated oncogene yki using the UAS/Gal4 expression system, which subsequently causes degeneration of the Indirect Flight Muscles (IFMs). Our preliminary study identified several target genes in IFMs that may mediate tumor sensitivity, but their roles require further validation through knockdown studies. However, simultaneously manipulating gene expression in the midgut and muscles requires two independent expression systems. In this study, we aim to adopt the LexA expression system to induce gut tumors while reserving UAS/Gal4 for regulating gene expression in the IFMs. This approach is challenging, as it requires integrating multiple genetic constructs into a single experimental fly. To achieve this, we applied traditional fly crosses to combine constructs located on different chromosomes. As proof of principle, we intend to knock down the gene cbt in the IFMs of flies with gut tumors. If successful, this experimental system will enable systematic screening of genetic factors involved in cancer-induced muscle wasting, providing valuable mechanistic insights.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Anton Bryantsev
Developing a Genetic Model to Study Cancer-induced Muscle Wasting
Colorectal tumors are often associated with debilitating skeletal muscle loss, leading to poor cancer patient survival. However, the exact mechanisms driving this effect remain unclear. To identify key genetic factors influencing muscle sensitivity to tumors, our lab uses the Drosophila fruit fly model. In our system, experimental tumors in the fly midgut are induced by overexpressing the mutated oncogene yki using the UAS/Gal4 expression system, which subsequently causes degeneration of the Indirect Flight Muscles (IFMs). Our preliminary study identified several target genes in IFMs that may mediate tumor sensitivity, but their roles require further validation through knockdown studies. However, simultaneously manipulating gene expression in the midgut and muscles requires two independent expression systems. In this study, we aim to adopt the LexA expression system to induce gut tumors while reserving UAS/Gal4 for regulating gene expression in the IFMs. This approach is challenging, as it requires integrating multiple genetic constructs into a single experimental fly. To achieve this, we applied traditional fly crosses to combine constructs located on different chromosomes. As proof of principle, we intend to knock down the gene cbt in the IFMs of flies with gut tumors. If successful, this experimental system will enable systematic screening of genetic factors involved in cancer-induced muscle wasting, providing valuable mechanistic insights.