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Title [sv]
Undersökning av nya funktioner för nyckelproteiner i onkogen TGFbeta och Wnt-signalering
Title [en]
Exploring novel functions of key components in oncogenic TGFbeta and Wnt-signaling
Abstract [en]
Prostate cancer (PC) is the second leading cause of cancer-related death in men. Due to lack of reliable biomarkers, many men with PC are overtreated while no curative options are available for patients progressing to castration-resistant PC (CRPC). The development of effective drugs is hampered by lack of knowledge about the molecular mechanisms behind metastatic progression of CRPC. Aberrant signals by Wnt and TGF? can potently promote invasion and metastasis. We have found that TRAF6 plays a key role in Wnt-signaling. Moreover, by studying how TGF? promotes invasion and metastasis of PC, we discovered that the receptor of TGF?; the transmembrane protein T?RI, undergoes TRAF6-dependent proteolytic cleavage in cancer cells. Consequently, T?RI is released from the cell membrane, and its intra-cellular domain (T?RI-ICD) can enter the nucleus, to promote transcription of invasive and metastatic genes to favor metastatic spreading. This important discovery makes it possible to specifically inhibit the pro-tumorigenic effects of TGF? while preserving normal TGF? signaling, to avoide the unwanted severe side effects of other drugs.  To drive progress beyond state-of the art, I will (I) explore novel treatment strategies directed against T?RI-ICD, using antibodies generated in collaboration with SciLifeLab DDDp, (II) explore the novel role of TRAF6 in Wnt signaling, and (III) analyze promising predictive biomarkers in clinical materials.
Principal InvestigatorLandström, Marene
Coordinating organisation
Umeå University
2020-01-01 - 2022-12-31
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
DiVA, id: project:2150Project, id: 2019-01598_VR