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.
Best presentation award, Blood Research Program, Research Day, 2021 Research Day, "Blood Research Program", November 2021 Sreoshee Rafiq received the best presentation award for her talk entitled "Chaperone-mediated autophagy regulation during acute promyelocytic leukemia differentiation". Her work describes that increased activity of chaperone-mediated autophagy (CMA), a subtype of autophagy, has a negative impact on differentiation therapy in acute myeloid leukemia cells.
Bern Cancer Research Cluster (BCRC) Research Retreat, 2021 The third BCRC retreat organized by D. Stroka, T. Marti and myself was a great success. We had eight fantastic summary talks on research success stories during the difficult pandemic situation. A total of 72 cancer researchers, 37 online and 35 onsite, participated in this years edition. We also officially announced the new "Tumor Biology Specialization Program" that initiated from our BCRC meetings. PhD students interested in cancer research can join this program to get the appropriate credit for their additional training in tumor biology. A big thank you to all BCRC members. Looking forward to our 4th BCRC retreat in 2022.
Poster Prize 11th Swiss Apoptosis and Autophagy Meeting (SA2M) 2021 Swiss Apoptosis and Autophagy Meeting (SA2M), onsite and online, 2021 Harpreet Mandhair won the poster prize of the French Autophagy Society CFATG for her short oral and poster presentation entitled "ULK complex blockade elicits NF-ҡB activation in GCB-DLBCL whilst augmenting cytotoxicity of Ibrutinib". Her work describes that autophagy inhibition using ULK1 inhibitors enhances Ibrutinib cytotoxicity in this aggressive lymphoma, despite and activation of NF-ҡB activation . This further underlines the complexity of combining autophagy modulating drugs with cytotoxic therapies.
Poster Prize Annual Meeting Life Sciences Switzerland (LS2) 2021 LS2 AM, Online, February 2021 Nicolas Niklaus won the FEBS poster prize for his short oral and poster presentation entitled "Oncogene-induced autophagy enhances migration and invasion of breast and prostate cancer cells". His work nicely shows how the oncogenic splice variant of the DMTF1 transcription factor, which is highly expressed in aggressive cancer cells, supports cellular migration and invasion via activation of autophagy.
CSL Behring Award for the best Master Thesis in Biomedical Sciences 2019 We congratulate Vera Imboden for winning the CSL Behring Award 2019 for her master thesis "Autophagy functions in immune-mediated thrombotic thrombocytopenic purpura (iTTP) pathology" under the supervision of PD Dr. M. Schaller (Hematology) and Prof. Dr. M. P. Tschan (Pathology).
Magali Humbert - TRTH Fellowship Winner December 2018 The Translational Research Training in Hematology (TRTH) is a joint effort of the European Hematology Association and the American Society of Hematology to provide mentoring to early-career hematological scientist. This highly competitive program selects 20 early-career scientists to receive advice from TRTH mentors to build-up a successful career in hematology research and to network at the two society meetings as well as during a one-week training. Magali Humbert (Group Tschan) was selected to participate in this one-year training in 2019 based on her work on chaperone-mediated autophagy in acute myeloid leukemia.
Grant: COST-STSM CA15138-39742 TRANSAUTOPHAGY 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.
Autophagy Team of the Month April, 2018 Recently, my autophagy team was presented as team of the month by the French Autophagy Association (Club francophone de l’autophagie - CFATG).
