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FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Epithelia and Human Cancer Cells


Due to their deregulation in cancer and their potential to be inhibited by small chemical compounds, tyrosine kinases are among the most important targets under consideration for cancer therapeutics. One such oncogenic tyrosine kinase is FAK, which is known to regulate cellular signalling downstream of Integrins and Receptor Tyrosine Kinases (RTK) at the cell surface. In this study, however, we report that FAK can act as a suppressor of oncogenic Receptor Tyrosine Kinases. This mechanism was observed in fruit fly tissues in vivo and human cancer-derived cells in vitro, which additionally suggests it is an evolutionary conserved mechanism in humans. FAK mediated this inhibition by controlling the sub-cellular localisation of receptors, via suppression of receptor recycling to the cell surface. These results suggest that in some particular cancer contexts such as RTK-driven tumours, FAK may act as a tumour suppressor and therefore, may not be a valid drug target.


Vyšlo v časopise: FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Epithelia and Human Cancer Cells. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004262
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004262

Souhrn

Due to their deregulation in cancer and their potential to be inhibited by small chemical compounds, tyrosine kinases are among the most important targets under consideration for cancer therapeutics. One such oncogenic tyrosine kinase is FAK, which is known to regulate cellular signalling downstream of Integrins and Receptor Tyrosine Kinases (RTK) at the cell surface. In this study, however, we report that FAK can act as a suppressor of oncogenic Receptor Tyrosine Kinases. This mechanism was observed in fruit fly tissues in vivo and human cancer-derived cells in vitro, which additionally suggests it is an evolutionary conserved mechanism in humans. FAK mediated this inhibition by controlling the sub-cellular localisation of receptors, via suppression of receptor recycling to the cell surface. These results suggest that in some particular cancer contexts such as RTK-driven tumours, FAK may act as a tumour suppressor and therefore, may not be a valid drug target.


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