TRIM-ing Ligand Dependence in Castration-Resistant Prostate Cancer

Patel, Lalit; Barton, Michelle C.

doi:10.1016/j.ccell.2016.05.014

Cited by 7 publications

(5 citation statements)

References 10 publications

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“…Nowadays, androgen deprivation therapy (ADT) is the mainstay therapy for advanced prostate cancer in addition to surgery . Although ADT is initially effective in suppressing tumor growth and survival, many prostate cancer patients will undergo recurrence and progress on anti‐androgen therapy, reaching a lethal stage termed castration‐resistant prostate cancer (CRPC) . There is an urgent need to explore the mechanisms of castration resistance, which will provide better intervention strategies for CRPC patients.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin‐6/signal transducer and activator of transcription 3 promotes prostate cancer resistance to androgen deprivation therapy via regulating pituitary tumor transforming gene 1 expression

et al. 2018

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Prostate cancer can progress from androgen dependence to androgen deprivation resistance with some unknown mechanisms. The current study aims to explore the possible role of pituitary tumor transforming gene1 (PTTG1) in castration‐resistant prostate cancer (CRPC). Initially, we found that PTTG1 expression was significantly increased in androgen‐independent prostate cancer cell lines PC3, DU145 and CRPC specimens compared with that in androgen‐dependent prostate cancer cell line LNCaP and initial prostate cancer specimens. PTTG1 overexpression significantly enhanced the cell survival rate, clonality and tumorigenicity in LNCaP cells upon androgen‐deprivation therapy (ADT). While knockdown of PTTG1 expression significantly elevated the sensitivity of DU145 cells to ADT. The effects of PTTG1 overexpression on LNCaP cells may be ascribed to the induced EMT and increased CD44+ CD24‐ cancer stem cell population. Furthermore, we detected that PTTG1 expression was regulated by interleukin‐6 via activated signal transducer and activator of transcription 3 (STAT3) directly binding to the region −500 to +1 of PTTG1 promoter in LNCaP cells. In conclusion, our results elucidate that interleukin‐6/STAT3 activation can increase PTTG1 expression and, consequently, promote the resistance to ADT in CRPC by inducing EMT and increasing the cancer stem cell population, suggesting that PTTG1 may be a novel therapeutic target for CRPC.

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Section: Introductionmentioning

confidence: 99%

“…progress on anti-androgen therapy, reaching a lethal stage termed castration-resistant prostate cancer (CRPC). 4 There is an urgent need to explore the mechanisms of castration resistance, which will provide better intervention strategies for CRPC patients.…”

mentioning

confidence: 99%

Interleukin‐6/signal transducer and activator of transcription 3 promotes prostate cancer resistance to androgen deprivation therapy via regulating pituitary tumor transforming gene 1 expression

et al. 2018

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“…Whereas monoubiquitination of AR by the ubiquitin E3 ligase RNF6 enhances its transcriptional activity in response to androgen treatment, AR poly-ubiquitination by other E3 ligases (i.e., CHIP and Mdm2) increases its turnover rate (Lin et al, 2002; Xu et al, 2009; Sarkar et al, 2014; Liu et al, 2016). AR also interacts physically with TRIM24, a RING-domain E3 ligase negatively regulating p53, which results in increased AR-dependent transcription (Patel & Barton, 2016), and TRIM24 was proposed to interact with PML (Zhong et al, 1999). AR was among the first transcription factors shown to be SUMOylated (Poukka et al, 2000), and a very recent work from Zhang et al shows that lack of AR sumoylation leads to epidydimal dysfunction and infertility in mice (Zhang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cells

et al. 2019

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Aberrant androgen signaling drives prostate cancer and is targeted by drugs that diminish androgen production or impede androgen–androgen receptor (AR) interaction. Clinical resistance arises from AR overexpression or ligand-independent constitutive activation, suggesting that complete AR elimination could be a novel therapeutic strategy in prostate cancers. IRC117539 is a new molecule that targets AR for proteasomal degradation. Exposure to IRC117539 promotes AR sumoylation and ubiquitination, reminiscent of therapy-induced PML/RARA degradation in acute promyelocytic leukemia. Critically, ex vivo, IRC117539-mediated AR degradation induces prostate cancer cell viability loss by inhibiting AR signaling, even in androgen-insensitive cells. This approach may be beneficial for castration-resistant prostate cancer, which remains a clinical issue. In xenograft models, IRC117539 is as potent as enzalutamide in impeding growth, albeit less efficient than expected from ex vivo studies. Unexpectedly, IRC117539 also behaves as a weak proteasome inhibitor, likely explaining its suboptimal efficacy in vivo. Our studies highlight the feasibility of AR targeting for degradation and off-target effects’ importance in modulating drug activity in vivo.

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“…Several TRIMs are involved in steroid hormone regulation [ 282 ]. TRIM24 was deemed a major effector of “AR reprogramming” [ 283 ] and contributed to castration-resistant prostate cancer (CRPC) [ 283 ]. In ER + breast cancer, TRIM39 [ 83 ] and TRIM29 knockdown significantly suppresse ER + breast cancer cell proliferation [ 79 ].…”

Section: The Trim Family and Cancer Pathologymentioning

confidence: 99%

TRIM family contribute to tumorigenesis, cancer development, and drug resistance

et al. 2022

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The tripartite-motif (TRIM) family represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases. TRIM family is involved in a variety of cellular signaling transductions and biological processes. TRIM family also contributes to cancer initiation, progress, and therapy resistance, exhibiting oncogenic and tumor-suppressive functions in different human cancer types. Moreover, TRIM family members have great potential to serve as biomarkers for cancer diagnosis and prognosis. In this review, we focus on the specific mechanisms of the participation of TRIM family members in tumorigenesis, and cancer development including interacting with dysregulated signaling pathways such as JAK/STAT, PI3K/AKT, TGF-β, NF-κB, Wnt/β-catenin, and p53 hub. In addition, many studies have demonstrated that the TRIM family are related to tumor resistance; modulate the epithelial–mesenchymal transition (EMT) process, and guarantee the acquisition of cancer stem cells (CSCs) phenotype. In the end, we havediscussed the potential of TRIM family members for cancer therapeutic targets.

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TRIM-ing Ligand Dependence in Castration-Resistant Prostate Cancer

Cited by 7 publications

References 10 publications

Interleukin‐6/signal transducer and activator of transcription 3 promotes prostate cancer resistance to androgen deprivation therapy via regulating pituitary tumor transforming gene 1 expression

Interleukin‐6/signal transducer and activator of transcription 3 promotes prostate cancer resistance to androgen deprivation therapy via regulating pituitary tumor transforming gene 1 expression

A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cells

TRIM family contribute to tumorigenesis, cancer development, and drug resistance

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