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Title [sv]
molekylär utvärdering av cellsignalering i tumörer
Title [en]
Molecular evaluation of cell signaling in tumors
Abstract [en]
A tumor does not consist of a homogenous population of cancer cells. Therefore, to understand cancer, the tumor microenvironment and the interplay between the different cell types present in the tumor have to be taken into account, as well as how this interplay regulates the growth and survival of cancer cells. This requires new methods that provide information on activity status of multiple signaling pathways in individual cells in tissues. We have developed several methods, such as in situ PLA and proxHCR, for visualization of protein-protein interactions at a single cell level. The aim of this project is to simultaneously analyze the activity status of multiple signaling networks at a single cell level, which will require assay development as well as further method development. Both the development of the individual in situ PLA assays and the further developments of the in situ PLA technology will be important deliverables by the herein described project, but the overarching goal is to combine these for a multiplexed assay to investigate tissue sections from tumors. The multiplexed in situ PLA assay developed herein will provide information on what networks are active in cancer cells, the crosstalk between pathways and how this is influenced by mutations. We also want to determine to what extent signaling varies depending on positioning within the tumor, to reveal how the surrounding non-malignant cells in the tumor microenvironment interact with the cancer cells.
Publications (1 of 1) Show all publications
Kermpatsou, D., Olsson, F., Wåhlén, E., Söderberg, O., Lennartsson, J. & Norlin, M. (2024). Cellular responses to silencing of PDIA3 (protein disulphide-isomerase A3): Effects on proliferation, migration, and genes in control of active vitamin D. Journal of Steroid Biochemistry and Molecular Biology, 240, Article ID 106497.
Open this publication in new window or tab >>Cellular responses to silencing of PDIA3 (protein disulphide-isomerase A3): Effects on proliferation, migration, and genes in control of active vitamin D
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2024 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 240, article id 106497Article in journal (Refereed) Published
Abstract [en]

The active form of vitamin D, 1,25-dihydroxyvitamin D3, is known to act via VDR (vitamin D receptor), affecting several physiological processes. In addition, PDIA3 (protein disulphide-isomerase A3) has been associated with some of the functions of 1,25-dihydroxyvitamin D3. In the present study we used siRNA-mediated silencing of PDIA3 in osteosarcoma and prostate carcinoma cell lines to examine the role(s) of PDIA3 for 1,25-dihydroxyvitamin D3-dependent responses. PDIA3 silencing affected VDR target genes and significantly altered the 1,25-dihydroxyvitamin D3-dependent induction of CYP24A1, essential for elimination of excess 1,25-dihydroxyvitamin D3. Also, PDIA3 silencing significantly altered migration and proliferation in prostate PC3 cells, independently of 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 increased thermostability of PDIA3 in cellular thermal shift assay, supporting functional interaction between PDIA3 and 1,25-dihydroxyvitamin D3-dependent pathways. In summary, our data link PDIA3 to 1,25-dihydroxyvitamin D3-mediated signalling, underline and extend its role in proliferation and reveal a novel function in maintenance of 1,25-dihydroxyvitamin D3 levels.
Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
PDIA3, 1, 25-dihydroxyvitaminD3, Cellular proliferation, VDR
National Category
Biochemistry Molecular Biology
Identifiers
urn:nbn:se:uu:diva-528689 (URN)10.1016/j.jsbmb.2024.106497 (DOI)001222646600001 ()38460707 (PubMedID)
Funder
Swedish Foundation for Strategic Research, SB16-0039Swedish Cancer Society, 19 0135Swedish Cancer Society, 21 1427 Pj 01HSwedish Research Council, 2017-01775
Available from: 2024-05-31 Created: 2024-05-31 Last updated: 2025-08-12Bibliographically approved
Principal InvestigatorSöderberg, Ola
Coordinating organisation
Uppsala University
Funder
Period
2017-12-01 － 2019-12-31
National Category
Cell and Molecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
DiVA, id: project:6102Project, id: 2017-01775_VR
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