Evolutionary conservation of Tino/Quaking interaction suggests its impact to cell polarity control in ontogenesis and oncogenesis

Loss of cell polarity is very common in invasive and metastatic tumours, but also in early stages of cancerogenesis. In C. elegans the conserved Par genes control several proteins transducing polarity cues in the embryo. One of these transducers is ceMex-3, a translational regulator of cell fate during development. Its human ortholog is Tino, firstly identified in our lab as a post-transcriptional regulator. The high conservation between ceMex-3 and Tino suggests that also Tino could have an impact on mammalian embryogenesis, cell polarity and cancer. Par-4 is a ceMex-3 translational regulator, its human ortholog Lkb1 is responsible, if mutated, for the Peutz-Jeghers cancer syndrome. Another liaison dangereuse co-involves ceMex-3 with Gld-1 gene, whose mammal ortholog is Quaking (Qki). Both ceMex-3 and Gld-1 co-regulate common targets and if mutated induce onset of teratomas during embryogenesis. Here we show that Qki contributes to the negative regulation of Tino, confirming our hypothesis of evolutive conservation of Tino pathway. Furthermore, identification of Tino's target mRNAs and their consensus reveals that 50% of these mRNAs contains also Qki consensus, underlying the possibility that Qki and Tino co-regulate common targets. Acknowledgements: research suported by AIRC, MUR (PRIN 2008), Università di Firenze, ECR Firenze and FCR Lucca.