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 SA was identified in this screen. Dmel\SA encodes encodes a subunit of the cohesin ring complex; there is a paralogous gene in Drosophila, SA-2. In an additional assay, clones of SA or SA-2 induced in epithelial tissue in a wild-type background (without a potentiating mutation) also showed invasive phenotypes.
A limited number of genetic reagents are available for SA including a loss-of-function mutation and several RNAi-targeting constructs. Multiple genetic reagents have been generated for SA-2 including loss-of-functions mutations, RNAi-targeting constructs, and an anoverexpression construct. SA-2 is expressed primarily in testis.
Dmel\SA is orthologous to three human genes, STAG1, STAG2, and STAG3. None of the human genes has been introduced into flies. Using a breast cancer cell line, the effects of knockdown of STAG1 or STAG2 were assessed; in both cases a significant increase in both invasion and migration was observed. The STAG3 gene was not tested in this assay.
[updated Nov. 2020 by FlyBase; FBrf0222196]
STAG1 and STAG2 encode components of the cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication; the cohesin complex may also play a role in spindle pole assembly during mitosis. [Gene Cards, STAG1, STAG2; 2020.11.28]
Many to many: 3 human genes to 2 Drosophila genes.
Many to many: 3 human genes to 2 Drosophila genes.
Moderate-scoring ortholog of human STAG1, STAG2, and STAG3 (2 Drosophila to 3 human). Dmel\SA-2 shares 24-25% identity and 42-44% similarity with the human genes.
High-scoring ortholog of human STAG1, STAG2, and STAG3 (2 Drosophila to 3 human). Dmel\SA shares 39-46% identity and 60-66% similarity with the human genes.