Fig. 1

Crypt fixation and chemoprevention with lithium treatment. APC = adenomatous polyposis coli tumor-suppressor gene. DKK2 = Dickkopf WNT Signaling Pathway Inhibitor 2. ISCs = intestinal stem cells. WIF1 = WNT Inhibitory Factor 1. ISCs reside at the bottom of the crypts of the epithelium of the colon where they engage in ongoing neutral competition with each other for a position in the crypt. These neutral dynamics are disturbed whenever an ISCs acquires a second mutation in the APC allele. APC-mutant ISCs have a competitive advantage by secreting Wnt antagonists (e.g. NOTUM, WIF1, DKK2) that drive the differentiation of WT ISCs, thereby resulting in mutant crypt fixation and the development of premalignant adenomas. In this study, we propose that boosting the Wnt pathway in WT ISCs using lithium diminishes this competitive advantage and prevents adenoma formation. This figure was created by using Adobe Illustrator 2022 (version 26.0.3)