SENP1 regulates PTEN stability to dictate prostate cancer development

Bawa-Khalfe, Tasneem; Yang, Feng-Ming; Ritho, Joan; Lin, Hui Kuan; Cheng, Jinke; Yeh, Edward T.H.

doi:10.18632/oncotarget.13283

Cited by 38 publications

(22 citation statements)

References 40 publications

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“…Mus81 SUMOylation is important for normal mitotic chromosome congression, and cells expressing SUMO-resistant Mus81 mutants exhibit compromised DNA damage responses related to tumorigenesis ( 80 ). SENP1 exhibits carcinogenic properties associated with the promotion of androgen receptor-dependent and -independent cell proliferation, the stabilization of hypoxia-inducible factor (HIF)1α, an increase in vascular endothelial growth factor (VEGF) expression and the support of angiogenesis ( 81 ). Ubc9, PIAS1 and SENP1 are highly expressed in human prostate cancer specimens and are associated with hypoxia-inducing factor 1alpha (HIF1α) expression, and SENP1 enhances prostate epithelial cell proliferation.…”

Section: Sumo and Cancermentioning

confidence: 99%

The post-translational modification, SUMOylation, and cancer (Review)

et al. 2018

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SUMOylation is a reversible post-translational modification which has emerged as a crucial molecular regulatory mechanism, involved in the regulation of DNA damage repair, immune responses, carcinogenesis, cell cycle progression and apoptosis. Four SUMO isoforms have been identified, which are SUMO1, SUMO2/3 and SUMO4. The small ubiquitin-like modifier (SUMO) pathway is conserved in all eukaryotes and plays pivotal roles in the regulation of gene expression, cellular signaling and the maintenance of genomic integrity. The SUMO catalytic cycle includes maturation, activation, conjugation, ligation and de-modification. The dysregulation of the SUMO system is associated with a number of diseases, particularly cancer. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis and apoptosis. SUMO can be used as a potential therapeutic target for cancer. In this review, we briefly outline the basic concepts of the SUMO system and summarize the involvement of SUMO proteins in cancer cells in order to better understand the role of SUMO in human disease.

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Section: Sumo and Cancermentioning

confidence: 99%

The post-translational modification, SUMOylation, and cancer (Review)

et al. 2018

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“…SENP1 expression is regulated both androgen dependent and independent, and increased SENP1 expression could also potentiate both androgen dependent and independent prostate cancer cells growth [20]. A recent study suggested that SENP1 could modulate the stability of the tumor suppressor gene PTEN to regulate prostate epithelial cell apoptosis [21]. SENP1 inhibits ubiquitylation and degradation of PTEN via deSUMOylation, which is similar to the case of CSR1.…”

Section: Discussionmentioning

confidence: 81%

Sumoylation Negatively Regulates CSR1-Dependent Prostate Cancer Cell Death

Luo

Liu

Wan

et al. 2018

Cell Physiol Biochem

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Background/Aims: SUMOylation is a dynamic process and reversed by the activity of SUMOspecific proteases (SENPs) family. SENP1, a member of this family, is highly expressed and plays oncogenic roles in diverse cancers including prostate cancer. However, the SENP1-transgenic mice exhibit aberrant transformation of the mouse prostate gland but do not develop cancer. Cellular Stress Response 1 (CSR1) is a tumor suppressor gene and frequently deleted in prostate cancers. Overexpression of CSR1 in prostate cancer cells inhibits colony formation, anchorage-independent growth and induces cell death. Methods: The relationship between CSR1 and SENP1 were determined by immunoprecipitation-based proteomics screen and verified by GST-pull down assay. In vivo SUMOylation assay was used to detect the direct effect of SENP1 in the regulation of CSR1. Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Senp1 −/− and CSR1 −/− PC3 cells. FACS assay was used to determine the apoptosis ratio of cells after transfection. Results: CSR1 is SUMOylated at K582 and rapid ubiquitinated and degradated in prostate cancer cells. SENP1 interacts with and deSUMOylates CSR1 to prevent its degradation and enhances CSR1-dependent prostate cancer cell death. Conclusion: Thus, our data indicates that CSR1 is a critical SUMOylated substrate of SENP1 that might partially explain the controversial roles of SENP1 in prostate cancer development.

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“…SENP1 regulates cell apoptosis in prostate epithelia. [12] The low levels of SENP1 were essential for the maintenance of stemness in osteosarcoma stem cells, and SENP1 overexpression led to a significant increase in the sensitivity of osteosarcoma stem cells to the herpes simplex virus 1 thymidine kinase gene in combination with ganciclovir in vitro and in vivo. SENP1 plays an important role in regulating genes that are important for cancer development and progression [13].…”

Section: Discussionmentioning

confidence: 98%

SENP1 Knockdown Suppresses Tumor Progression in Lung Adenocarcinoma by Regulating AAR Genes Expression

Chen¹,

Li²,

Yu³

et al. 2020

Preprint

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Background SUMO specific peptidase 1(SENP1) is an important factor involved in the regulation of small ubiquitin-related modifier (SUMO) modification. Our previous research has shown that SENP1 could be a potential tumor-promoting factor in non-small cell lung cancer (NSCLC). However, its role in tumor progression remains largely unknown. This study aims to characterize the role of SENP1 in lung adenocarcinoma. Methods The TCGA database provided us expression profiles of SENP1 and overall survival rates. loss-of-function assays were performed to examine the effect of SENP1 on proliferation, migration and invasion of lung adenocarcinoma cells in vitro and in vivo. Immunoprecipitation (IP), western blot and quantitative real time PCR (qRT-PCR) were carried out to reveal the interrelation between SENP1, SIRT6 and AAR (amino acid response) genes signal pathway. Results In this study, we found that SENP1 was expressed at high levels in lung adenocarcinoma tissues and advanced TNM stages and was significantly associated with poor prognosis. we also found that SENP1 knockdown inhibited lung adenocarcinoma cell progression in vitro and in vivo. SUMOylation of SIRT6 was also observed in lung adenocarcinoma, and it was reduced by SENP1. SUMOylation of SIRT6 specifically increased its deacetylation of histone H3 on lysine 56 instead of that of lysine 9 (H3K9) in an in vitro model. Mechanistically, we found that knockdown of SENP1 reduced the expression of AAR genes by decreasing H3K56 acetylation through increasing SIRT6 SUMOylation. Moreover, mutation of the SUMOylation sites of Sirt6 reduced its tumor-suppressive effects. Conclusions These results revealed that SENP1 promotion of tumor progression in lung adenocarcinoma and its tumor-promoting effects might be attributed to its important role in the regulation of Sirt6 SUMOylation and the expression of AAR genes.

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SENP1 regulates PTEN stability to dictate prostate cancer development

Cited by 38 publications

References 40 publications

The post-translational modification, SUMOylation, and cancer (Review)

The post-translational modification, SUMOylation, and cancer (Review)

Sumoylation Negatively Regulates CSR1-Dependent Prostate Cancer Cell Death

SENP1 Knockdown Suppresses Tumor Progression in Lung Adenocarcinoma by Regulating AAR Genes Expression

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