LKB1, gardien de la prolifération hépatocytaire et de l’intégrité génomique

Abstract : Liver Kinase B1 (LKB1) is involved in pleiotropic biological processes and known to be a key regulator of hepatic metabolism and polarity. Here, we investigated the contribution of LKB1 in hepatocyte proliferation and liver regeneration process. We demonstrated that loss of hepatic Lkb1 promotes liver mass recovery, through an increase of hepatocytes proliferation, independently on metabolic/energetic balance. LKB1 regulates G0/G1 progression, specifically by controlling Epidermal Growth Factor Receptor (EGFR) signaling. In addition, later during regeneration, LKB1 controls mitotic fidelity. Deletion of Lkb1 results in major alterations of mitotic spindle formation, along the polarity axis, independently of AMP- activated protein kinase (AMPK) activity, a key target of LKB1. Consequently, LKB1 deficiency leads to an alteration of ploidy profile, at late stage of regenerative process. Overall our study highlights the dual role of LKB1, during liver regeneration, as a guardian of hepatocyte proliferation and genomic integrity.
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Vanessa Maillet. LKB1, gardien de la prolifération hépatocytaire et de l’intégrité génomique. Biologie cellulaire. Université Sorbonne Paris Cité, 2017. Français. ⟨NNT : 2017USPCB103⟩. ⟨tel-02134173⟩

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