TGF-β signaling - Tumor biology in prostate cancer
Prostate cancer is the most common tumor in men in the Western society and the incidence is expected to increase. However, we still lack good molecular tools to identify aggressive prostate cancer. This is a reason why many men with prostate cancer need to undergo radical prostatectomy with the risk of severe complications.
Our aim is to identify the molecular signaling pathways leading to advanced prostate cancer. This knowledge will be used to design novel therapeutic strategies and improved molecular diagnostic tools.
Our research is focused on TGFβ signal transduction, tumor biology and molecular pathology, particularly in prostate cancer. TGFβ plays an important role for regulation of migration and invasion in several kinds of cancer cells, including prostate cancer cells.
In aggressive prostate cancer there is a correlation between the amount of secreted TGFβ and poor prognosis with development of metastases. We have found that the ubiquitin-ligase TRAF6 is a crucial co-regulator of TGFβ-induced non-canonical and oncogenic responses, as it associates with the TGFβ type I receptor. TRAF6 promotes also expression and activation of proteolytic enzymes, such as TACE and presenilin1, which cleaves the TGFβ type I receptor to liberate its intracellular domain (ICD). The generated ICD translocate to the nucleus in an unknown manner, where it contributes to gene transcription of pro-invasive and metastatic genes. We focus our research on exploring how TGFβ regulates invasive and metastatic behavior of prostate cancer cells. We have access to unique collections of biobanked material at Biobanken Norr in collaboration with reseachers here in Umeå.
We collaborate with the Ludwig Institute for Cancer Research, Uppsala Branch www.licr.uu.se, where we in detail, study molecular mechanisms whereby TGFβ regulates specific oncogenic cellular responses. See our annual report for the Apoptotic Signaling Group on www.licr.uu.se.
We collaborate with SciLifeLab Drug Discovery Platform in order to design novel and more specific cancer drugs.