Cancer Autophagy Group

My research team investigates molecular mechanisms involved in the survival of acute myeloid leukemia cells (AML). Currently, we are deciphering the function of alternative splicing, the non-metabolic functions of glycolytic enzymes and autophagy recycling pathway in AML cell survival. Additional research projects address the function of autophagy in cell migration and metastasis of breast cancer cells. All these pre-clinical studies in targeted, personalized cancer therapy are conducted in close collaboration with clinical pathologists and the Translational Research Unit.

Current research projects

Unravel the functions of autophagy in breast cancer motility

Group Tschan Metastasis formation accounts for the majority of deaths from breast cancer, making it imperative to better understand the mechanisms driving the metastatic cascade in order to develop therapeutic interventions to target it. We earlier discovered an oncogenic splice variant of a transcription factor and named it DMTF1β. We now show that DMTF1β promotes invasion and tumor-initiating capacity of breast cancer cells by activating autophagy. It has also been shown that inhibition of autophagy can have undesirable effects in some cancer types and induce epithelial to mesenchymal transition (EMT), one of the early steps of metastasis. Our aim is to identify breast cancer subtypes or cellular conditions in which autophagy inhibition will decrease migration, and those in which the inhibition of autophagy will promote invasiveness.


Cancer-associated fibroblast from breast cancer patient

PU.1 and alternative splicing

Group Tschan The transcription factor PU.1 (SPI1) plays a key role in myeloid differentiation as well as in myeloid cell survival. Aberrant low PU.1 expression contributes to an immature myeloid phenotype, e.g., acute myeloid leukemia (AML). Interestingly, two studies indicate that high PU.1 protein levels were associated with alternative splicing promoted by either direct binding to splice factors or by RNA binding. Our data indicate that PU.1 controls splicing of the anti-apoptotic CFLAR (cFLIP) gene, and thereby regulates cell death during myeloid differentiation.



Schematic representation of how PU.1 might regulate splicing of the anti-apoptotic gene CFLAR

Reducing FASN expression facilitates AML differentiation

Group Tschan Apart from glycolysis and OXPHOS, lipid metabolism is frequently reprogrammed in leukemic cells to support cellular growth. Particularly, the protein important for de novo lipid synthesis, fatty acid synthase (FASN), is frequently upregulated in tumor cells. We found that high FASN expression in acute myeloid leukemia (AML) cells is associated with an immature hematopoietic phenotype. Decreasing FASN levels by RNAi or epigallocatechin-3-gallate (EGCG) treatment, but no blocking its enzymatic function, resulted in improved response of AML cells to differentiation therapy.



FASN localizes at the lysosome (LAMP1) to increase mTOR activity. NB4 APL cells were differentiated towards neutrophils with all-trans retinoid acid (ATRA)


Travel Grant Award 10th French Autophagy Meeting (CFATG) 2022

French Autophagy Meeting (CFATG), 2022, Besançon

Jun Xu won a travel grant award to attend the annual meeting of the French Autophagy Society CFATG for his short oral presentation entitled "BNIP3L/NIX, a downstream effector of oncogene-induced cancer cell autophagy and invasion". His work describes how the oncogenic splice variant of the transcription factor DMTF1 activates autophagy in cancer cells paralleled by increased cellular migration.


Oslo, February, 2018
Sarah Parejo: In this short-term scientific mission, I had the opportunity to visit Norway and to learn how to perform the LDH sequestration assay in the laboratory of Dr. Nikolai Engedal at the Centre of Molecular Medicine in Oslo. Furthermore, we carried out experiments to advance our project on ALK-inhibition in EML4-ALK positive lung cancer cells. The results we obtained demonstrate that targeting ALK with Ceritinib stimulates autophagic activity in our model, suggesting a potential role of autophagy in drug resistance to ALK targeted therapies in lung cancer. My six week stay in Oslo was truly an exciting and instructive experience. I was able to benefit from the great expertise of Nikolai Engedal and his lab members, and we will implement the LDH assay in our laboratory in Bern.


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