APC and obesity due to melanocortin 4 receptor deficiency: The crucial role of Apc inactivation and dysregulation of Wnt/β-catenin signaling in obesity is shown in a study demonstrating that inactivation of Pten in Lgr5+ ISCs, whether alone or in combination with obesity, is insufficient to drive adenoma formation in mice, but combination of Pten deletion with Apc loss increases tumor burden and worsens survival (87).