Abstract PR06: Spatial sequestration of GSKα as a cellular response to amino acid starvation

The ability of cells to tolerate amino acid starvation is fundamental to survival under stress. Some cancer cells are vulnerable to asparagine depletion, which is exploited therapeutically using asparaginase. We recently found that Wnt pathway activation induces a profound therapeutic vulnerability to asparaginase in acute leukemia and in colorectal cancer (Hinze et al., In press; Hinze et al., 2019). This effect is mediated by a β-catenin independent branch of Wnt signaling termed Wnt-dependent stabilization of proteins (Wnt/STOP), which inhibits GSK3-dependent protein degradation. Asparaginase resistance is uniquely dependent on GSK3α because its inhibition fully phenocopied Wnt-induced sensitization to asparaginase (p Citation Format: Laura Hinze, Sabine Schreek, Andre Zeug, Evgeni Ponimaskin, Roxane Labrosse, James Degar, Beat Bornhauser, Jean-Pierre Bourquin, Martin Stanulla, Alejandro Gutierrez. Spatial sequestration of GSKα as a cellular response to amino acid starvation [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PR06.