CARD14; MALT1; prostate cancer; protease; tumour cell survival; Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology (all); General Biochemistry, Genetics and Molecular Biology
Abstract :
[en] Prostate cancer (PCa) is one of the most common cancer types in men and represents an increasing global problem due to the modern Western lifestyle. The signalling adapter protein CARD14 is specifically expressed in epithelial cells, where it has been shown to mediate NF-κB signalling, but a role for CARD14 in carcinoma has not yet been described. By analysing existing cancer databases, we found that CARD14 overexpression strongly correlates with aggressive PCa in human patients. Moreover, we showed that CARD14 is overexpressed in the LNCaP PCa cell line and that knockdown of CARD14 severely reduces LNCaP cell survival. Similarly, knockdown of BCL10 and MALT1, which are known to form a signalling complex with CARD14, also induced LNCaP cell death. MALT1 is a paracaspase that mediates downstream signalling by acting as a scaffold, as well as a protease. Recent studies have already indicated a role for the scaffold function of MALT1 in PCa cell growth. Here, we also demonstrated constitutive MALT1 proteolytic activity in several PCa cell lines, leading to cleavage of A20 and CYLD. Inhibition of MALT1 protease activity did not affect PCa cell survival nor activation of NF-κB and JNK signalling, but reduced expression of cancer-associated genes, including the cytokine IL-6. Taken together, our results revealed a novel role for CARD14-induced signalling in regulating PCa cell survival and gene expression. The epithelial cell type-specific expression of CARD14 may offer novel opportunities for more specific therapeutic targeting approaches in PCa.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vanneste, Domien ✱; Université de Liège - ULiège > GIGA > GIGA I3 - Immunophysiology ; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Staal, Jens ✱; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Haegman, Mira; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Driege, Yasmine; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Carels, Marieke; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Van Nuffel, Elien; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
De Bleser, Pieter; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium ; Unit of Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium
Saeys, Yvan; Unit of Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, 9000 Ghent, Belgium
Beyaert, Rudi ✱; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Afonina, Inna S ✱; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
✱ These authors have contributed equally to this work.
Language :
English
Title :
CARD14 Signalling Ensures Cell Survival and Cancer Associated Gene Expression in Prostate Cancer Cells.
FWO - Flemish Research Foundation [BE] Stichting tegen Kanker [BE] CRIG - Cancer Research Institute Ghent [BE] UGent - Ghent University [BE]
Funding text :
Research in the authors’ lab is supported by the VIB, the Excellence of Science (EOS) Programme from the Fund for Scientific Research Flanders (FWO) (G0I1422N), the Foundation against Cancer (FAF-F/2016/812), Ghent University (BOF19/GOA/004). I.S.A. holds a fundamental mandate of the Foundation against Cancer and was supported by a proof of concept grant from the Cancer Research Institute Ghent (CRIG).
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