LKB1 signaling is activated in CTNNB1 -mutated HCC and positively regulates β-catenin-dependent CTNNB1 -mutated HCC

International audienceCTNNB1‐mutated HCC. They were found to be well‐differentiated, almost never steatotic, and often cholestatic, with a microtrabecular or acinar growth pattern. Here, we investigated whether LKB1, which controls energy metabolism, cell polarity, and cell growth, mediates the specific phenotype of CTNNB1‐mutated HCC. The LKB1 protein was overexpressed in CTNNB1‐mutated HCC and oncogenic activation of β‐catenin in human HCC cells induced the post‐transcriptional accumulation of the LKB1 protein encoded by the LKB1 (STK11) gene. Hierarchical clustering, based on the expression of a murine hepatic liver Lkb1 (Stk11) signature in a human public dataset, identified a HCC cluster, composed of almost all the CTNNB1‐mutated HCC, that expresses a hepatic liver LKB1 program. This was confirmed by RT‐qPCR of an independent cohort of CTNNB1‐mutated HCC and the suppression of the LKB1‐related profile upon β‐catenin silencing of CTNNB1‐mutated human hepatoma cell lines. Previous studies described an epistatic relationship between LKB1 and CTNNB1 in which LKB1 acts upstream of CTNNB1. Thus, we also analyzed the consequences of Lkb1 deletion on the zonation of hepatic metabolism, known to be the hallmark of β‐catenin signaling in the liver. Lkb1 was required for the establishment of metabolic zonation in the mouse liver by positively modulating β‐catenin signaling. We identified positive reciprocal cross talk between the canonical Wnt pathway and LKB1, both in normal liver physiology and during tumorigenesis that likely participates in the amplification of the β‐catenin signaling by LKB1 and the distinctive phenotype of the CTNNB1‐mutated HCC

Int J Public Health

OBJECTIVES: Despite the healthy migrant effect, immigrants and descendants of immigrants face health challenges and socio-economic difficulties. The objective of this study is to examine the perinatal health of women of migrant origin. METHODS: The nationwide French ELFE (Etude Longitudinale Francaise Depuis l'Enfance) birth cohort study recruited approximately 18,000 women. We studied pre-pregnancy BMI, gestational diabetes mellitus (GDM), as well as tobacco, and alcohol consumption during pregnancy according to migrant status and region of origin. RESULTS: Women from North Africa and Turkey had a higher risk of pre-pregnancy overweight and GDM, while women from Eastern Europe and Asia had a lower risk of pre-pregnancy overweight and obesity, but a higher risk of GDM compared to non-immigrants. Women from Sub-Saharan Africa had a higher risk of being overweight or obese pre-pregnancy. Compared to non-immigrants, immigrants-but not descendants of immigrants-had lower levels of tobacco smoking, while descendants of immigrants were less likely to drink alcohol during pregnancy. CONCLUSIONS: Pregnant women of migrant origin have particular health needs and should benefit from a medical follow-up which addresses those needs