Utforskande av signalvägar som regleras av Transforming Groth Factor Beta och TRAF6 i prostatacancer

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Tittel [sv]

Utforskande av signalvägar som regleras av Transforming Groth Factor Beta och TRAF6 i prostatacancer

Tittel [en]

EXPLORING SIGNALING PATHWAYS IN PROSTATE CANCER REGULATED BY TRANSFORMING GROWTH FACTOR BETA AND TRAF6

Abstract [en]

Westudy the function of the serine-threonine kinase; TGFB type I receptor (TBRI)/ubiquitin-ligase TRAF6-complex, in signal transduction pathways in cancer cells. TRAF6 specify intracellular routing and function of TBRI, via posttranslational modification (PTM) adding Lys63-linked poly-ubiquitin chains to TBRI. ThisPTM promotes TBRI proteolytic cleavage, via TRAF6-induced activation of specific cutting enzymes, generating a liberated intracellular domain (ICD), which enters the nucleus. We will study the role TRAF6/TBRI-ICD to regulate transcription (have TBRI enzymatic activity in the nucleus? is TBRI-ICD acting as a transcription factor?), migration and invasion of cancer cells. We have generated monoclonal antibodies (mabs; designed by us), which prevent cleavage of TBRI. Weobserve that treatment with mabs of mice with a human xenograft orthotopic prostate model, prevented invasion and metastasis of cancer cells,suggesting that novel cancer drugs can be developed based on our findings. We collaborate with SciLifeLab DDP in order to test novel antibodies, which might be useful as novel cancer drugs. We will also investigate novel functions of Smad7for its activity as a potential transcription factor (identified by us), to regulate activity of c-Jun. We use biochemical, cell and molecular biology methods, advanced confocal imaging, animal models and tumor tissues, to explore biological functions of TBRI-ICD, TRAF6and Smad7/DNA-complexes, in tumor progression.

Principal InvestigatorLandström, Marene Umeå universitet

Koordinerande organisasjon

Umeå universitet

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Vetenskapsrådet

Tidsperiod

2016-01-01 － 2019-12-31

HSV kategori

Cell and Molecular BiologyCancer and OncologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)