HMMR promotes prostate cancer proliferation and metastasis via AURKA/mTORC2/E2F1 positive feedback loop DOI Creative Commons
Kaixuan Guo, Cheng Liu,

Juanyi Shi

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Feb. 7, 2023

Abstract Although dysregulated HMMR is linked to prostate cancer (PCa) prognosis, the precise mechanisms remain unclear. Here, we sought elucidate role of in PCa progression as well underlying mechanism. Herein, found that upregulation frequently observed samples and was associated with poor prognosis. Additionally, significantly promoted proliferation metastasis through gain- loss-of function approaches vitro vivo. Mechanistically, may interact AURKA elevated protein level inhibiting ubiquitination-mediated degradation, which subsequently activated mTORC2/AKT pathway ensure reinforcement progression. Moreover, upregulated E2F1 caused from sustained activation turn transcription factor promote transcription, thereby forming a positive feedback loop trigger Importantly, administration mTOR inhibitor partially antagonised HMMR-mediated In summary, not only reveal novel possible post-translation mechanism mediated by involved regulation, but also describe contributes deterioration, suggesting serve potential promising therapeutic target PCa.

Language: Английский

Prostate Cancer: A Journey Through Its History and Recent Developments DOI Open Access

Hamza Mallah,

Zania Diabasana,

Sina Soultani

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 194 - 194

Published: Jan. 9, 2025

Prostate cancer is one of the most common diseases among men worldwide and continues to pose a serious threat health. This review shows history new developments in management prostate cancer, with an emphasis on range therapeutic approaches, such as hormone therapy, radiation surgery, innovative targeted therapeutics. The evolution these treatments examined light clinical outcomes, patient quality life, emerging resistance mechanisms, recently shown vitamin D-based strategies. New that have potential increase survival rates reduce side effects are also discussed, including PARP inhibitors (PARPis), immunotherapy, tailored medication. Additionally, use biomarkers sophisticated imaging methods decision-making explored, focus how tools might improve care. absolute necessity for multidisciplinary approach improving treatment strategies becoming more apparent our understanding biology deepens. ensures patients receive customized medicines fit their unique profiles. Future avenues investigation will resolving issues dealing efficacy results, ultimately leading disease cure patients.

Language: Английский

Citations

1
Prognostic value of circulating Chromogranin A in prostate cancer: a systematic review and meta-analysis DOI Creative Commons
Xiaoying Tang, Zhenyu Liu,

Liangdong Song

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 5, 2025

Background There are discrepancies between the results of different studies regarding prognostic role circulating Chromogranin A (CgA) in prostate cancer. Therefore, we conducted a meta-analysis available findings to explore value prognosis Methods We systematically searched PubMed, Embase, Web Science, Cochrane Library, and Clinical Trials databases for on relationship CgA survival outcomes cancer from inception until December 2024, focused articles detecting CgA, with primary endpoints being overall (OS), progression-free (PFS). Results Of 2049 retrieved, 10 met our inclusion criteria, involving total 1445 patients. Elevated was associated poorer OS (HR=1.82, 95% CI: 1.38–2.41; p<0.001) PFS (HR=2.04, 1.42–2.94; p<0.001). However, no correlation found post-treatment changes (HR=0.95, 0.66–1.37; p=0.767). Conclusion Circulating is predictive marker poor sample size current study small larger needed further validate this future.

Language: Английский

Citations

1
The role of transcription factors in prostate cancer progression DOI Open Access
Jongeun Lee, Yoontae Lee

Molecules and Cells, Journal Year: 2025, Volume and Issue: unknown, P. 100193 - 100193

Published: Feb. 1, 2025

Prostate cancer is one of the most common malignancies in men, with cases initially responding to androgen deprivation therapy (ADT). However, a significant number patients eventually develop castration-resistant prostate (CRPC), an aggressive form disease. Although AR pathway inhibitors target receptor (AR) signaling, and have extended survival CRPC, prolonged treatment can lead emergence neuroendocrine (NEPC), lethal subtype characterized by expression markers reduced activity. The transition from adenocarcinoma NEPC driven lineage plasticity, wherein cells adopt phenotype evade treatment. Consequently, face poor clinical outcomes limited effective options. To improve outcomes, it crucial understand molecular mechanisms driving development. In this review, we highlight role transcription factors process explore their potential as therapeutic targets.

Language: Английский

Citations

1
Novel hormone therapies for advanced prostate cancer: understanding and countering drug resistance DOI Creative Commons
Zhipeng Wang, Jie Wang,

Dengxiong Li

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101232 - 101232

Published: Feb. 1, 2025

Language: Английский

Citations

1
Tumor Microenvironment and Cancer Metastasis DOI Creative Commons
Yulong Li, Han Wu

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

The tumor microenvironment is a complex ecosystem composed of diverse cell types, extracellular matrix components, growth factors, and cytokines. dynamic interactions within this not only facilitate but also contribute to the establishment metastatic niches in distant organs. Furthermore, presence specific TME components can either promote or inhibit cancer migration, underscoring importance targeting these elements therapeutic strategies. This review seeks elucidate critical influence on metastasis examines potential targeted approaches. By integrating recent research insights, offers thorough understanding interplay between metastasis, serving as valuable reference for future investigations.

Language: Английский

Citations

1
Chemotherapy in metastatic castration-resistant prostate cancer: Current scenario and future perspectives DOI
Vicenç Ruiz de Porras, Albert Font, Àlvaro Aytés

et al.

Cancer Letters, Journal Year: 2021, Volume and Issue: 523, P. 162 - 169

Published: Sept. 11, 2021

Language: Английский

Citations

45
Lipid Metabolism and Epigenetics Crosstalk in Prostate Cancer DOI Open Access

Juan Carlos Triviño Pardo,

Vicenç Ruiz de Porras, Joan Gil

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(4), P. 851 - 851

Published: Feb. 18, 2022

Prostate cancer (PCa) is the most commonly diagnosed malignant neoplasm in men Western world. Localized low-risk PCa has an excellent prognosis thanks to effective local treatments; however, despite incorporation of new therapeutic strategies, metastatic remains incurable mainly due disease heterogeneity and development resistance therapy. The mechanisms underlying progression therapy are multiple include metabolic reprogramming, especially relation lipid metabolism, as well epigenetic remodelling, both which enable cells adapt dynamic changes tumour. Interestingly, metabolism epigenetics interconnected. Metabolism can regulate through direct influence metabolites on processes, while control by directly or indirectly regulating expression genes. Moreover, epidemiological studies suggest association between a high-fat diet, alter availability metabolites, progression. Here, we review alterations PCa, before focusing that connect them. We also discuss diet this scenario. This information may help identify prognostic predictive biomarkers targetable vulnerabilities.

Language: Английский

Citations

33
Anti-Androgen Receptor Therapies in Prostate Cancer: A Brief Update and Perspective DOI Creative Commons
Jian Huang,

Biyun Lin,

Benyi Li

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: March 10, 2022

Prostate cancer is a major health issue in western countries and the second leading cause of death American men. depends on androgen receptor (AR), transcriptional factor critical for prostate growth progression. Castration by surgery or medical treatment reduces levels, resulting prostatic atrophy regression. Thus, metastatic cancers are initially managed with deprivation therapy. Unfortunately, rapidly relapse after castration therapy progress to disease stage called castration-resistant (CRPC). Currently, clinical CRPCs focused suppressing AR activity antagonists like Enzalutamide reducing production Abiraterone. In practice, these treatments fail yield curative benefit CRPC patients part due gene mutations splicing variations, reactivation. It conceivable that eliminating protein cells promising solution provide potential outcome. Multiple strategies have emerged, several potent agents reduce levels were reported eliminate xenograft tumor preclinical models via distinct mechanisms, including proteasome-mediated degradation, heat-shock inhibition, suppression, blockage nuclear localization, N-terminal suppression. A few small chemical compounds undergoing trials combined existing antagonists. elimination enhanced mRNA degradation realistic avoiding reactivation during cancers.

Language: Английский

Citations

32
Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity DOI Creative Commons

Thomas C. Westbrook,

Xiangnan Guan,

Eva S. Rodansky

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 15, 2022

Abstract The androgen receptor (AR) signaling inhibitor enzalutamide (enza) is one of the principal treatments for metastatic castration-resistant prostate cancer (CRPC). Several emergent enza clinical resistance mechanisms have been described, including lineage plasticity in which tumors manifest reduced dependency on AR. To improve our understanding resistance, herein we analyze transcriptomes matched biopsies from men with CRPC obtained prior to treatment and at progression ( n = 21). RNA-sequencing analysis demonstrates that does not induce marked, sustained changes tumor transcriptome most patients. However, three patients’ show evidence plasticity. transcription factor E2F1 pathways linked stemness are highly activated baseline patients whose undergo We find a gene signature enriched these strongly associated poor survival independent patient cohorts risk castration-induced patient-derived xenograft models, suggesting harboring this expression program may be particular mediated by outcomes.

Language: Английский

Citations

31
A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1 DOI Creative Commons
Shuai Yuan,

Shaohua He,

Luyao Li

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 6, 2023

Abstract SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene progression and castration resistance of prostate cancer through N6-methyladenosine (m 6 A) reader YTHDC1 transcription factor HOXB13. We have shown level was increased in cancer, comparison its normal counterparts, further elevated castration-resistant (CRPC). The enhanced expression mRNA associated with neuroendocrine (NEPC) poor survival cancer. Furthermore, demonstrated promoted development addition cell proliferation migration. Interestingly, detected nucleus formed complex nuclear m A YTHDC1, which turn upregulated HOXB13 progression. Therefore, our findings reveal how cotransporter promotes provide therapeutic opportunity for apply neurological disorder drug inhibitors.

Language: Английский

Citations

22