Refereed journal article or data article (A1)

The PIM1 kinase promotes prostate cancer cell migration and adhesion via multiple signalling pathways




List of Authors: Niina M. Santio, Maria Salmela, Heidi Arola, Sini K.Eerola, Jyrki Heino, Eeva-Marja Rainio, Päivi J.Koskinen

Publisher: Academic Press

Publication year: 2016

Journal: Experimental Cell Research

Journal name in source: EXPERIMENTAL CELL RESEARCH

Journal acronym: EXP CELL RES

Volume number: 342

Issue number: 2

Number of pages: 12

ISSN: 0014-4827

eISSN: 1090-2422

DOI: http://dx.doi.org/10.1016/j.yexcr.2016.02.018

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/2933532


Abstract

The ability of cells to migrate and form metastases is one of the fatal hallmarks of cancer that can be conquered only with better understanding of the molecules and regulatory mechanisms involved. The oncogenic PIM kinases have been shown to support cancer cell survival and motility, but the PIM-regulated pathways stimulating cell migration and invasion are less well characterized than those affecting cell survival. Here we have identified the glycogen synthase kinase 3 beta (GSK3B) and the forkhead box P3 (FOXP3) transcription factor as direct PIM targets, whose tumour-suppressive effects in prostate cancer cells are inhibited by PIM-induced phosphorylation, resulting in increased cell migration. Targeting GSK3B is also essential for the observed PIM-enhanced expression of the prostaglandin-endoperoxide synthase 2 (PTGS2), which is an important regulator of both cell migration and adhesion. Accordingly, selective inhibition of PIM activity not only reduces cell migration, but also affects integrin-mediated cell adhesion. Taken together, these data provide novel mechanistic insights on how and why patients with metastatic prostate cancer may benefit from therapies targeting PIM kinases, and how such approaches may also be applicable to inflammatory conditions



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Last updated on 2022-05-10 at 15:01