PIM1 accelerates prostate cancer cell motility by phosphorylating actin capping proteins

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Santio , N M , Vainio , V , Hoikkala , T , Mung , K L , Lång , M , Vahakoski , R , Zdrojewska , J , Coffey , E T , Kremneva , E , Rainio , E-M & Koskinen , P J 2020 , ' PIM1 accelerates prostate cancer cell motility by phosphorylating actin capping proteins ' , Cell Communication and Signaling , vol. 18 , no. 1 , 121 . https://doi.org/10.1186/s12964-020-00618-6

Title: PIM1 accelerates prostate cancer cell motility by phosphorylating actin capping proteins
Author: Santio, Niina M.; Vainio, Veera; Hoikkala, Tuuli; Mung, Kwan Long; Lång, Mirka; Vahakoski, Riitta; Zdrojewska, Justyna; Coffey, Eleanor T.; Kremneva, Elena; Rainio, Eeva-Marja; Koskinen, Päivi J.
Contributor: University of Helsinki, Institute of Biotechnology
Date: 2020-08-08
Language: eng
Number of pages: 18
Belongs to series: Cell Communication and Signaling
ISSN: 1478-811X
URI: http://hdl.handle.net/10138/321333
Abstract: Background: The PIM family kinases promote cancer cell survival and motility as well as metastatic growth in various types of cancer. We have previously identified several PIM substrates, which support cancer cell migration and invasiveness. However, none of them are known to regulate cellular movements by directly interacting with the actin cytoskeleton. Here we have studied the phosphorylation-dependent effects of PIM1 on actin capping proteins, which bind as heterodimers to the fast-growing actin filament ends and stabilize them. Methods: Based on a phosphoproteomics screen for novel PIM substrates, we have used kinase assays and fluorescence-based imaging techniques to validate actin capping proteins as PIM1 substrates and interaction partners. We have analysed the functional consequences of capping protein phosphorylation on cell migration and adhesion by using wound healing and real-time impedance-based assays. We have also investigated phosphorylation-dependent effects on actin polymerization by analysing the protective role of capping protein phosphomutants in actin disassembly assays. Results: We have identified capping proteins CAPZA1 and CAPZB2 as PIM1 substrates, and shown that phosphorylation of either of them leads to increased adhesion and migration of human prostate cancer cells. Phosphorylation also reduces the ability of the capping proteins to protect polymerized actin from disassembly. Conclusions: Our data suggest that PIM kinases are able to induce changes in actin dynamics to support cell adhesion and movement. Thus, we have identified a novel mechanism through which PIM kinases enhance motility and metastatic behaviour of cancer cells.
Subject: PIM kinases
Capping proteins
CAPZ
Actin
Migration
Prostate cancer
D-BINDING-PROTEIN
ALPHA-SUBUNIT
KINASE
REGULATORS
MORPHOLOGY
IDENTIFICATION
EXPRESSION
MIGRATION
1182 Biochemistry, cell and molecular biology
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