Figure 9. Liver inflammation is critical for β-catenin–induced liver tumorigenesis.

Oncogenic activation of β-catenin in hepatocytes triggers an intrinsic inflammatory program with both pro- and antiinflammatory mediators that together construct an inflammatory microenvironment that controls tumor progression. In Apc-deficient (Apc^–/–) hepatocytes, β-catenin signaling is constitutively activated and induced: (a) the expression of a proinflammatory program resulting from both a direct control by the Wnt/β-catenin signaling and an indirect control by NF-κB that is not yet understood and (b) the expression of an antiinflammatory program including at least the direct LECT2 target gene. 2 interconnected factors relay the antiinflammatory response, the chemokine-like factor LECT2 and the iNKT cells. iNKT cell homeostasis is controlled by LECT2 at the level of liver homing and cytokine polarization. Together, the β-catenin–induced liver microenvironment exhibits a low grade of chronic inflammation that preserves an immune response with antitumor activity. In mice deficient in Apc and LECT2 (Apc^–/–LECT2^–/–), the lack of LECT2 causes high-grade inflammation in the liver microenvironment, which strongly potentiates the tumoral process and results in lung metastases (see Results).