CYLD regulates cell ferroptosis through Hippo/YAP signaling in prostate cancer progression

Prostate cancer (PCa) is one of the most common malignancy in men. However, the molecular mechanism of its pathogenesis has not yet been elucidated. In this study, we demonstrated that CYLD, a novel deubiquitinating enzyme, impeded PCa development and progression via tumor suppression. First, we fou...

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Published in:Cell death & disease 2024-01, Vol.15 (1), p.79-79, Article 79
Main Authors: Gu, Yanan, Wu, Shiqi, Fan, Junjie, Meng, Zeji, Gao, Guoqiang, Liu, Tianjie, Wang, Qi, Xia, Huayu, Wang, Xinyang, Wu, Kaijie
Format: Article
Language:English
Subjects:
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Antibodies
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell Proliferation
Deubiquitinating Enzyme CYLD
Ferroptosis
Heterografts
Humans
Immunology
Life Sciences
Male
Malignancy
Molecular modelling
Prostate
Prostate cancer
Prostatic Neoplasms - genetics
Tumor suppression
Tumor suppressor genes
Tumors
Ubiquitination
Yes-associated protein
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Summary:Prostate cancer (PCa) is one of the most common malignancy in men. However, the molecular mechanism of its pathogenesis has not yet been elucidated. In this study, we demonstrated that CYLD, a novel deubiquitinating enzyme, impeded PCa development and progression via tumor suppression. First, we found that CYLD was downregulated in PCa tissues, and its expression was inversely correlated with pathological grade and clinical stage. Moreover, we discovered that CYLD inhibited tumor cell proliferation and enhanced the sensitivity to cell ferroptosis in PCa in vitro and in vivo, respectively. Mechanistically, we demonstrated that CYLD suppressed the ubiquitination of YAP protein, then promoted ACSL4 and TFRC mRNA transcription. Then, we demonstrated that CYLD could enhance the sensitivity of PCa xenografts to ferroptosis in vivo. Furthermore, we discovered for the first time that there was a positive correlation between CYLD expression and ACSL4 or TFRC expression in human PCa specimens. The results of this study suggested that CYLD acted as a tumor suppressor gene in PCa and promoted cell ferroptosis through Hippo/YAP signaling.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-024-06464-5