Protein (CG10080) involved in “cell competition.”
Proto-oncogenes: Proto-oncogenes are proteins that help to regulate cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products. A proto-oncogene become an oncogene due to mutations or increased expression. The resultant protein is termed an oncoprotein. Oncoproteins are tumor-inducing agents. In organisms many abnormal cells normally undergo a programmed form of death called apoptosis. However activated oncogenes can cause those cells to survive and proliferate producing cancerous tumors. This process by which normal cells are transformed into cancer cells is called carcinogenesis.
Carcinogenesis arises from the activation of oncoproteins and/or inactivation of tumor suppressor proteins like the lethal giant larvae (Lgl) in flies and mammals. During the initial stage of carcinogenesis, transformation occurs in a single epithelial cell that grows within an epithelial monolayer. However, it remains unclear what happens at the interface between normal and transformed epithelial cells during this process. In Drosophila (fruit flies), it has been shown that normal and transformed cells often compete with each other for survival in an epithelial tissue, in a process called “cell competition.” However the molecular mechanisms whereby “loser cells” undergo apoptosis are not clearly understood.
Protein (CG10080) involved in “cell competition”
Now researchers Yoichiro Tamori and Associate Professor Wu-Min Deng of Florida State University and Yasuyuki Fujita of University College London have examined the involvement of lethal giant larvae (Lgl) in cell competition and shown that a novel Lgl-binding protein is involved in Lgl-mediated cell competition. Using biochemical immunoprecipitation methods, they first identified protein (CG10080) as the novel binding partner of Lgl in both flies and mammals. They called protein (CG10080) Mahjong a Chinese game in which winners and losers are determined through strong competition.
These researchers have demonstrated that Mahjong is involved in cell competition in both flies and mammals. In particular, they found that canine kidney epithelial cells depleted for Mahjong undergo apoptosis, but only when surrounded by non-transformed cells. According to the researchers this is the first evidence that cell competition can occur in a mammalian cell culture system.
At present the researchers are not clear what molecules/signaling pathways are regulated by Lgl/Mahjong during cell competition. But they hope that future studies might reveal important pathway components that could be targeted therapeutically to prevent tumor cells from “winning” in their race against normal tissue cells.
Source: http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000422
July 14, 2010