SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling‐mediated tumorigenesis by enhancing β‐catenin biosynthesis

Abstract

Abstract Wnt/β‐catenin signalling is widely implicated in embryogenesis, tissue homeostasis and tumorigenesis. The key event in Wnt signalling activation is β‐catenin accumulation, which is controlled by both its production and degradation. However, much more emphasis has been placed on the understanding of its degradation. Here, we show that the synthesis of β‐catenin protein, which requires a group of serine/arginine‐rich splicing factors (SRSF), also contributes to its tumorigenic activity. Overexpression of SRSF1 and SRSF9 promote β‐catenin accumulation via the recruitment of β‐catenin mRNA and by enhancing its translation in an mTOR‐dependent manner. We further demonstrate that, like SRSF1, SRSF9 is also an oncogene, and is frequently overexpressed in multiple types of human tumours. Finally, our results suggest that promoting degradation and blocking production of β‐catenin synergistically reduce β‐catenin levels under pathological conditions and that a combinational therapy could be a promising approach for the treatment of cancer patients.

Keywords

• β‐catenin synthesis
• oncogene
• SRSF1
• SRSF9
• Wnt signalling