Sumoylation Negatively Regulates CSR1-Dependent Prostate Cancer Cell Death

Luo, Huarong; Liu, Ying; Wan, Xiaoyang; Li, Junliang; Wu, Min; Zhang, Qimin; Wu, Denglong; Zhao, Xin; Wang, Tian-Ru

doi:10.1159/000489370

Cited by 6 publications

(3 citation statements)

References 21 publications

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“…Modulating SENP1 level dictates colony formation of prostate cancer cell lines, tumor growth in nude mice and also prostate cancer cell migration and invasion (40). SENP1 interacts with and deSUMOylates CSR1 to prevent its degradation and enhances CSR1-dependent prostate cancer cell death (41). Herein, we present evidence that MT inhibits the proliferation of LNCaP cells by decreasing the expression of SENP1, which is required for the full activation of ARs.…”

Section: Introductionmentioning

confidence: 81%

Melatonin decreases androgen-sensitive prostate cancer growth by suppressing SENP1 expression

Lin¹,

Dong²,

Zhang³

et al. 2022

Transl Androl Urol

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Background: Melatonin is a hormone naturally produced by the pineal gland in the brain. In addition to modulating circadian rhythms, it has pleiotropic biological effects including antioxidant, immunomodulatory, and anti-cancer effects. Herein, we report that melatonin has the ability to decrease the growth and metastasis of androgen-dependent prostate cancer.Methods: To evaluate the anti-cancer effect of melatonin on androgen-sensitive prostate cancer in vitro or in vivo, the effects of cell proliferation, apoptosis, migration and invasion were analyzed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry, Transwell assay, and immunohistochemistry (IHC), respectively. Next, the interaction between androgen receptor (AR) and SUMO specific protease 1 (SENP1) was detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting, and confirmed by luciferase reporter assay. Furthermore, the Small Ubiquitin-like Modifier (SUMO) proteins are a group of small proteins that are covalently attached to and detached from other proteins in cells to modify their function.(SUMOylation) of histone deacetylases 1 (HDAC1) was measured by proximity ligation assay (PLA). Results:The treatment of melatonin cripples the transcriptional activity of AR, which is essential for the growth of the androgen-dependent prostate cancer cell, LNCaP. The lower activity of AR was dependent on melatonin induced SUMOylation of HDAC1, which has been established as a key factor for the transcriptional activity of AR. Mechanistically, the effect of melatonin on AR was due to the decreased SENP1 protein level and the subsequent increased HDAC1 SUMOylation level. The overexpression of SENP1 abrogated the anti-cancer ability of melatonin on LNCaP cells.Conclusions: These findings indicate that melatonin is a suppressor of androgen-dependent prostate cancer tumorigenesis.

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Section: Introductionmentioning

confidence: 81%

Melatonin decreases androgen-sensitive prostate cancer growth by suppressing SENP1 expression

Lin¹,

Dong²,

Zhang³

et al. 2022

Transl Androl Urol

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“…Finally, based on the report that the SCARA3 promoter region is hyper-methylated in prostate cancer [ 13 ], there is a possibility that hyper-methylation is also present in lung cancer. In addition, sumoylation of the K582 region of SCARA3 can reduce protein stability [ 43 ]. Therefore, there is a need to analyze SCARA3 promoter methylation and study sumoylation of SCARA3 protein in lung cancer treatment using SCARA3 expression regulation.…”

Section: Discussionmentioning

confidence: 99%

SCARA3 inhibits cell proliferation and EMT through AKT signaling pathway in lung cancer

2022

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Background Scavenger receptor class A member 3 (SCARA3) is decreased in prostate cancer and myeloma. However, functions of SCARA3 in various cancers remain unclear. In this study, we tried to evaluate the functional study of SCARA3 in lung cancer. Methods The expression level of SCARA3 in the TCGA-database, lung cancer tissue microarray and lung cancer cells and the prognosis of lung cancer patients were measured. Lung cancer tissue microarray was analyzed pathologically using immunohistochemistry, and quantitative analysis of SCARA3 in normal lung cells and lung cancer cells was analyzed using western blot analysis. Survival curves for lung cancer patients were prepared with the Kaplan-Meier method. Migration and invasion of SCARA3 overexpressed lung cancer cells were determined using a Transwell chamber system. Proliferation of lung cancer cells was determined based on cell viability assay using cell culture in vitro and a tumorigenicity model of BALB/C nude mouse in vivo. Results The expression of SCARA3 was abnormally reduced in TCGA-database, lung tissue microarray, and various lung cancer cells. However, overexpression of SCARA3 reduced the proliferation of lung cancer. The ability of SCARA3 to inhibit cancer cell proliferation was maintained even in vivo using a mouse xenograft model. In addition, overexpression of SCARA3 reduced migration and invasion ability of lung cancer cells and induced decreases of EMT markers such as β-catenin, vimentin, and MMP9. We aimed to prove the role of SCARA3 in the treatment of Lung cancer, and shown that the expression level of SCARA3 is important in cancer treatment using cisplatin. The enhancement of the effect of cisplatin according to SCARA3 overexpression is via the AKT and JNK pathways. Conclusions This study confirmed an abnormal decrease in SCARA3 in lung cancer. Overexpression of SCARA3 potently inhibited tumors in lung cancer and induced apoptosis by increasing sensitivity of lung cancer to cisplatin. These results suggest that SCARA3 is a major biomarker of lung cancer and that the induction of SCARA3 overexpression can indicate an effective treatment.

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“…Additionally, they have shown that mutation of newly identified SUMO modification sites of USP39 further promotes the proliferation-enhancing effect of USP39 on prostate cancer cells. Among the SUMOylated proteins in prostate cancer are the driving proteins such as AR [134,263,[265][266][267][268][269][270], PTEN [271], p53 [216,272], ATF3 [273], FOXA1 [274], FOXA2 [275], CSR1 [276], TBL1 and TBLR1 [277], WWOX [278], pontin [279] SLUG [280], and SNAIL1 [281]. Two SUMOylation residues (K386 and K520) are defined in AR [134].…”

Section: Sumoylationmentioning

confidence: 99%

Post-Translational Modifications That Drive Prostate Cancer Progression

Samaržija

2021

Biomolecules

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While a protein primary structure is determined by genetic code, its specific functional form is mostly achieved in a dynamic interplay that includes actions of many enzymes involved in post-translational modifications. This versatile repertoire is widely used by cells to direct their response to external stimuli, regulate transcription and protein localization and to keep proteostasis. Herein, post-translational modifications with evident potency to drive prostate cancer are explored. A comprehensive list of proteome-wide and single protein post-translational modifications and their involvement in phenotypic outcomes is presented. Specifically, the data on phosphorylation, glycosylation, ubiquitination, SUMOylation, acetylation, and lipidation in prostate cancer and the enzymes involved are collected. This type of knowledge is especially valuable in cases when cancer cells do not differ in the expression or mutational status of a protein, but its differential activity is regulated on the level of post-translational modifications. Since their driving roles in prostate cancer, post-translational modifications are widely studied in attempts to advance prostate cancer treatment. Current strategies that exploit the potential of post-translational modifications in prostate cancer therapy are presented.

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Sumoylation Negatively Regulates CSR1-Dependent Prostate Cancer Cell Death

Cited by 6 publications

References 21 publications

Melatonin decreases androgen-sensitive prostate cancer growth by suppressing SENP1 expression

Melatonin decreases androgen-sensitive prostate cancer growth by suppressing SENP1 expression

SCARA3 inhibits cell proliferation and EMT through AKT signaling pathway in lung cancer

Post-Translational Modifications That Drive Prostate Cancer Progression

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