Institut de recherché en cancerologie de Montpellier – IRCM
Campus Val D’Aurelle
34298 Montpellier cedex 5
Website Antonio Maraver
”Uncovering the role of Flavin-containing monooxygenase 4 in lung adenocarcinoma: a new protector against ferroptosis”
During the characterization of a new mouse model of lung adenocarcinoma developed in our lab, we revealed a largely unknown protein in lung cancer, the flavin-containing monooxygenase (FMO) 4. We first demonstrated that FMO4 is highly expressed in tumor samples vs healthy lung tissue in four different genetic engineered mouse models that together cover 50% of the oncogenic driver mutations in human lung adenocarcinoma. We then showed that FMO4 is highly expressed in human lung cancer, it is amplified in 3 to 8% of patients with lung adenocarcinoma, and its expression correlates with poor survival in a subset of lung adenocarcinoma patients. We also found that reactive oxidative species (ROS) induced FMO4 expression and that FMO4 knock-down strongly decreases growth of human lung adenocarcinoma cell lines with concomitant increase in ROS levels. More specifically, FMO4 loss of function sensitizes to ferroptosis, a specific cell death with important implications in immunotherapy. Finally, we revealed the critical role of FMO4 during human bronchoalveolar cell transformation in vitro and in vivo. In summary, we identified FMO4 as a new tumor promoter protein in lung adenocarcinoma protecting against ferroptosis.
Host: Emilio CASANOVA
Contact for questions: Helmut KUBISTA