In Drosophila, the Ras85DV12 activated RAS mutation produces overproliferation phenotypes, but typically does not result in phenotypes indicative of metastasis (see FBhh0000474). In a screen for loss-of-function mutations that, in combination with this activated RAS mutation, induce invasive tumors, the Drosophila tetraspanin gene Tsp29Fb was identified. Tetraspanins mediate signal transduction events, in part by regulating the trafficking and function of other membrane proteins. Other tetraspanin genes in human have been implicated in the development of cancer, including CD9, CD82, CD151 and TSPAN8.
Tsp29Fb is one of 37 or 38 tetraspanin genes in flies; there are 33 tetraspanin genes in human. Dmel\Tsp29Fb and its close paralogs (Dmel\Tsp29Fa, Dmel\Tsp47F, Dmel\Tsp39D) comprise a group most closely related to 3 genes in human: CD63, TSPAN6, and TSPAN7. A UAS construct of the Hsap\CD63 has been introduced into flies, but has not been characterized.
Dmel\Tsp29Fb has not been well characterized; two RNAi-targeting constructs have been generated. In experiments using various different GAL4 drivers for RNAi-mediated knockdown, knockdown of Tsp29Fb itself results in reduced tissue growth. However, in Ras85DV12 expressing tissue, it enhances RAS-driven tumor growth and invasion. It is postulated that Tsp29Fb is necessary for maintaining epithelial cell polarity, acting via EGFR signaling: loss-of-function clones result in phenotypes in the retinal epithelium; Tsp29Fb interacts genetically with scrib, dlg1 and Egfr.
See also human disease model reports 'cancer, multiple, RAS-related' (FBhh0000474) and 'cancer, epithelial, Scribble-complex-related' (FBhh0000586).
[updated Oct. 2019 by FlyBase; FBrf0222196]
Other tetraspanin genes in human in human have been implicated in the development of cancer: evidence suggests that CD9 and CD82 are suppressors of metastasis, whereas CD151 and TSPAN8 promote metastasis (Charrin et al., 2014; pubmed:25128561).
There are 33 tetraspanin genes in human ( https://www.genenames.org/data/genegroup/#!/group/768 ).
Tetraspanins (TSP) have four transmembrane domains and two extracellular loops containing specific short motifs, including highly conserved cysteine residues. TSPs are thought to function as scaffolds that bring multiple proteins, including other TSPs, membrane-associated proteins, extracellular and cytosolic proteins, into single membrane region (FBgg0000532).
Tetraspanin proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility.
Tetraspanins play a key role in regulating the trafficking and function of other membrane proteins (Charrin et al., 2014; pubmed:25128561).
Low-scoring ortholog of human CD63, TSPAN6, and TSPAN7 (many to many; multiple paralogs and orthologs in both species). Dmel\Tsp29Fb shares 27-30% identity and 49-50% similarity with the human genes.
High-scoring ortholog of human genes KRAS, HRAS, and NRAS (many to many; multiple paralogs and orthologs in both species). Dmel\Ras85D shares 78-86% identity and 86-92% similarity with KRAS, HRAS, and NRAS; for these three human genes, Ras85D is the highest-scoring ortholog in Drosophila.