Unconventional function of the glycolytic enzyme HK3 in AML cell survival Group Tschan Elevated HK3 expression levels are characteristic of monocytic AML. Notably, high HK3 expression correlates with reduced initial responsiveness and the development of secondary resistance to the BCL2 antagonist venetoclax. We propose that HK3 promotes AML cell survival and attenuates therapeutic responses through non-metabolic mechanisms. HK3 expression in AML cells is associated with intrinsic resistance to venetoclax (ABT-199)
Cancer-associated fibroblast (CAF) autophagy Group Tschan Desmoplasia is characterized by the excessive deposition of extracellular matrix (ECM) components, such as collagen, and is associated with increased tumor aggressiveness. Cancer-associated fibroblasts (CAFs) are major contributors to desmoplastic remodeling. Our ITMP collaborative research team will investigate the potential role of CAF autophagy in this process. Modulating autophagy in breast cancer CAFs
Function and post-translational regulation of the oncogenic splice variant DMTF1β Group Tschan We found that knocking down the oncogenic DMTF1β isoform reduces migration and invasion of prostate and breast cancer cells. Interestingly, this was accompanied by the downregulation of autophagy-related pathways and autophagic flux. Mechanistically, we identified the autophagy protein ULK1 as a novel interaction partner of DMTF1β, whereby DMTF1β promoted ULK1 protein stability. Additionally, we discovered that DMTF1β is a short-lived protein that undergoes polyubiquitination in a β-domain-specific manner, leading to proteasomal degradation. β-specific domain DTMF1β is associated with poly-ubiquitination
