This report is based upon experiments in Drosophila designed to identify genes involved in later stages of cancer development, including cellular acquisition of invasive behavior. The Drosophila gene shot was identified in this screen. Dmel\shot encodes a member of the plakin protein family, large proteins that link cytoskeletal elements to each other and to specialized sites at the plasma membrane. Multiple genetic reagents including classical loss-of-functions mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for shot.
There are two genes orthologous to Dmel\shot in human, DST and MACF1. Neither genes has been introduced into flies. Using a breast cancer cell line, the effect of knockdown of DST was assessed; a significant increase in both invasion and migration was observed. The MACF1 gene was not tested in this assay.
[updated Nov. 2020 by FlyBase; FBrf0222196]
Plakins are giant-sized (200–800 kDa) modular proteins that link cytoskeletal elements to each other and to specialized sites at the plasma membrane. Maintaining such linkages lends mechanical strength to cells and tissue structures and ensures proper cellular development. [https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/plakin; 2020.11.28]
DST encodes a member of the plakin protein family of adhesion junction plaque proteins. The DST protein act as a cytoskeletal linker protein and as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. [Gene Cards, DST; 2020.11.28]