
CARD14 signalling ensures cell survival and cancer associated gene expression in prostate cancer cells
- Author
- Domien Vanneste, Jens Staal (UGent) , Mira Haegman (UGent) , Yasmine Driege (UGent) , Marieke Carels (UGent) , Elien Van Nuffel, Pieter De Bleser (UGent) , Yvan Saeys (UGent) , Rudi Beyaert (UGent) and Inna Afonina (UGent)
- Organization
- Project
- Abstract
- 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-kappa B 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-kappa B and INK 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.
- Keywords
- CARD14, MALT1, protease, prostate cancer, tumour cell survival, NF-KAPPA-B, MALT1, ACTIVATION, MUTATIONS, INFLAMMATION, COMPLEX, TARGET, AXIS
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8766320
- MLA
- Vanneste, Domien, et al. “CARD14 Signalling Ensures Cell Survival and Cancer Associated Gene Expression in Prostate Cancer Cells.” BIOMEDICINES, vol. 10, no. 8, 2022, doi:10.3390/biomedicines10082008.
- APA
- Vanneste, D., Staal, J., Haegman, M., Driege, Y., Carels, M., Van Nuffel, E., … Afonina, I. (2022). CARD14 signalling ensures cell survival and cancer associated gene expression in prostate cancer cells. BIOMEDICINES, 10(8). https://doi.org/10.3390/biomedicines10082008
- Chicago author-date
- Vanneste, Domien, Jens Staal, Mira Haegman, Yasmine Driege, Marieke Carels, Elien Van Nuffel, Pieter De Bleser, Yvan Saeys, Rudi Beyaert, and Inna Afonina. 2022. “CARD14 Signalling Ensures Cell Survival and Cancer Associated Gene Expression in Prostate Cancer Cells.” BIOMEDICINES 10 (8). https://doi.org/10.3390/biomedicines10082008.
- Chicago author-date (all authors)
- Vanneste, Domien, Jens Staal, Mira Haegman, Yasmine Driege, Marieke Carels, Elien Van Nuffel, Pieter De Bleser, Yvan Saeys, Rudi Beyaert, and Inna Afonina. 2022. “CARD14 Signalling Ensures Cell Survival and Cancer Associated Gene Expression in Prostate Cancer Cells.” BIOMEDICINES 10 (8). doi:10.3390/biomedicines10082008.
- Vancouver
- 1.Vanneste D, Staal J, Haegman M, Driege Y, Carels M, Van Nuffel E, et al. CARD14 signalling ensures cell survival and cancer associated gene expression in prostate cancer cells. BIOMEDICINES. 2022;10(8).
- IEEE
- [1]D. Vanneste et al., “CARD14 signalling ensures cell survival and cancer associated gene expression in prostate cancer cells,” BIOMEDICINES, vol. 10, no. 8, 2022.
@article{8766320, abstract = {{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-kappa B 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-kappa B and INK 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.}}, articleno = {{2008}}, author = {{Vanneste, Domien and Staal, Jens and Haegman, Mira and Driege, Yasmine and Carels, Marieke and Van Nuffel, Elien and De Bleser, Pieter and Saeys, Yvan and Beyaert, Rudi and Afonina, Inna}}, issn = {{2227-9059}}, journal = {{BIOMEDICINES}}, keywords = {{CARD14,MALT1,protease,prostate cancer,tumour cell survival,NF-KAPPA-B,MALT1,ACTIVATION,MUTATIONS,INFLAMMATION,COMPLEX,TARGET,AXIS}}, language = {{eng}}, number = {{8}}, pages = {{15}}, title = {{CARD14 signalling ensures cell survival and cancer associated gene expression in prostate cancer cells}}, url = {{http://doi.org/10.3390/biomedicines10082008}}, volume = {{10}}, year = {{2022}}, }
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