03 December 2020
Cell signalling pathway implicated in cancer formation
Published online 22 January 2014
Cellular signalling pathways help maintain a fine balance between the growth of new cells and how they differentiate into a particular type of cell during embryonic development. When these signals go awry, this control can be lost and cancer can result.
A study led by Daisuke Yamamoto of the Tohoku University Graduate School of Life Sciences, Sendai, Japan, and including Beston Nore of the University of Sulaimani in the Kurdistan Region of Iraq, has characterized a signal that controls the proliferation of germ cells in the ovary of the fruit fly Drosophila melanogaster.
The signal transducing molecule Btk29A halts the proliferation of germ cells by phosphorylating specific tyrosine residues in the protein β-catenin,prompting it to act as a transcription factor. Mutations in the Btk29A gene led to over-proliferation of germ cells causing ovarian tumours to form. The human counterpart of this gene encodes Bruton's tyrosine kinase (Btk), mutations of which cause the heritable immunodeficiency disease XLA and various lymphomas.
β-catenin has been implicated in a range of cancers, due to its role integrating various signalling pathways. These novel interactions with Btk29A therefore have wider implications than just within the Drosophila ovary.
"This discovery will open up a new avenue for inventions of novel therapies for cancer treatment via the manipulation of hitherto unknown Btk-dependent external signals to block the proliferation of cancer cells," says Daisuke Yamamoto.
- Hamada-Kawaguchi, N. et al. Btk29A Promotes Wnt4 Signaling in the Niche to Terminate Germ Cell Drosophila. Science (17 January 2014) doi:10.1126/science.1244512