The lipid droplet in cancer: From being a tumor‐supporting hallmark to clinical therapy

Acta Physiologica, Journal Year: 2024, Volume and Issue: 240(3)

Published: Jan. 22, 2024

Abstract Introduction Abnormal lipid metabolism, one of the hallmarks in cancer, has gradually emerged as a novel target for cancer treatment. As organelles that store and release excess lipids, droplets (LDs) resemble “gears” facilitate development body. Aim This review discusses life cycle LDs, relationship between abnormal LDs hallmarks, application theragnostic clinical contexts to provide contemporary understanding role cancer. Methods A systematic literature search was conducted PubMed SPORTDiscus. Retrieve summarize trials drugs proteins associated with LD formation using Clinical Trials website. Create schematic diagram tumor microenvironment Adobe Illustrator. Conclusion top ten metabolism caused by excessive generation interrelates other hallmarks. The crosstalk intracellular free fatty acids (FFAs) promotes an inflammatory environment supports growth. Moreover, contribute metastasis cell death resistance vivo. Statins, HMGCR inhibitors, are promising be pioneering commercially available anti‐cancer formation.

Language: Английский

---

Suppression of dopamine receptor 2 inhibits the formation of human prostate cancer PC‑3‑derived cancer stem cell‑like cells through AMPK inhibition

Oncology Letters, Journal Year: 2025, Volume and Issue: 29(3)

Published: Jan. 14, 2025

Cancer stem cells (CSCs) contribute to the resistance of intractable prostate cancer, and dopamine receptor (DR)D2 antagonists exhibit anticancer activity against cancer CSCs. Human PC-3 were used generate CSC-like cells, serving as a surrogate system identify specific DR subtype inhibition which significantly affects prostate-derived Additionally, present study aimed determine downstream signaling molecules this that exert more profound effects compared with other subtypes. The inhibitory or small interfering (si)RNAs on subtypes by analyzing morphological changes expression patterns pluripotency markers, cell growth activities in vitro invasion. L-741,626, DRD2 antagonist, induced PC-3-derived suppressed Oct4 (a marker), inhibited tumors. proliferation heterozygous null generated using CRISPR/Cas9 method, was slow, their sphere-forming ability substantially reduced, indicating diminished capacity produce In addition, phosphorylation AMPK siRNA knockout may be putative molecule involved production maintenance cells. Specific suppression caused lose properties formation followed AMPK, is considered DRD2. Further understanding mechanisms regulates provide valuable insights into identification molecular targets for treating wherein constitutively activated.

Language: Английский

---

A novel lncRNA FLJ promotes castration resistance in prostate cancer through AR mediated autophagy

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 3, 2025

Progression to castration resistance is the leading cause of death in prostate cancer patients. Long non-coding RNAs (lncRNAs) have recently become a focal point regulation development. However, few lncRNAs associated with castration-resistant (CRPC) been reported. Firstly, we explore CRPC by RNA sequencing and validated using quantitative polymerase chain reaction (qRT-PCR) fluorescence situ hybridization (RNA-FISH). The clinical significance FLJ was evaluated collected cohort. Functional loss assays were performed assess effects on cells both vitro vivo. regulatory mechanism investigated immunohistochemistry (IHC), qRT-PCR, dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assays. highly expressed higher stages Gleason scores cancer. strongly positively correlated androgen receptor (AR), which acts as transcription factor directly binds promoter region enhance its transcription. Knockdown inhibits cell proliferation increases sensitivity enzalutamide (ENZA) vitro. Mechanistically, promotes inhibiting AR nuclear import cytoplasmic protein degradation, thereby activating androgen-independent signaling pathway. Importantly, vivo experiments showed that knockdown inhibited tumor growth enhanced therapeutic effect ENZA. This study identifies novel lncRNA progression. Sustained activation upregulate expression. circumvents traditional androgen-dependent survival entry Targeting FLJ-AR axis may represent strategy for patients

Language: Английский

---

Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2309 - 2309

Published: April 14, 2023

Prostate cancer (PCa) is the second most frequent type of in men worldwide, with 288,300 new cases and 34,700 deaths estimated United States 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination these. In advanced cases, androgen-deprivation therapy (ADT) considered first-line therapy; however, PCa patients eventually progresses to castration-resistant prostate (CRPC) despite ADT. Nonetheless, transition from androgen-dependent androgen-independent tumors not yet fully understood. The physiological processes epithelial-to-non-epithelial (“mesenchymal”) (EMT) mesenchymal-to-epithelial (MET) are essential normal embryonic development; they have also been linked higher tumor grade, metastatic progression, treatment resistance. Due this association, EMT MET identified as important targets novel therapies, including CRPC. Here, we discuss transcriptional factors signaling pathways involved EMT, addition diagnostic prognostic biomarkers that these processes. We tackle various studies conducted bench bedside current landscape EMT-targeted therapies.

Language: Английский

---

Cancer-associated fibroblasts and prostate cancer stem cells: crosstalk mechanisms and implications for disease progression

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 18, 2024

Graphical Abstract Created using Biorender.com .

Language: Английский

---

Prostate Cancer Stem Cells: Biology and Treatment Implications

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14890 - 14890

Published: Oct. 4, 2023

Stem cells differentiate into mature organ/tissue-specific at a steady pace under normal conditions, but their growth can be accelerated during the process of tissue healing or in context certain diseases. It is postulated that proliferation and carcinomas are sustained by presence vital cellular compartment resembling stem residing tissues: 'stem-like cancer cells' (CSCs). Mutations prostate lead to formation cancer. Prostate CSCs (PCSCs) have been identified partially characterized. These express surface markers include CD44, CD133, integrin α2β1, pluripotency factors like OCT4, NANOG, SOX2. Several signaling pathways also over-activated, including Notch, PTEN/Akt/PI3K, RAS-RAF-MEK-ERK HH. Moreover, PCSCs appear induce resistance radiotherapy chemotherapy, while has linked aggressive behavior higher relapse rates. The development treatment policies target tumors appealing as through cell killing, trigger tumor repopulation via activated cells. Thus, blocking this reactive mobilization may facilitate positive outcome cytotoxic treatment.

Language: Английский

---

Biomolecular fingerprints of the effect of zoledronic acid on prostate cancer stem cells: Comparison of 2D and 3D cell culture models

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 753, P. 109920 - 109920

Published: Feb. 1, 2024

Language: Английский

---

Analysis of genetic biomarkers, polymorphisms in ADME-related genes and their impact on pharmacotherapy for prostate cancer

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: Oct. 19, 2023

Abstract Prostate cancer (PCa) is a non-cutaneous malignancy in males with wide variation incidence rates across the globe. It second most reported cause of death. Its etiology may have been linked to genetic polymorphisms, which are not only dominating casualties but also exerts significant effects on pharmacotherapy outcomes. Although many therapeutic options available, suitable candidates identified by useful biomarkers can exhibit maximum efficacy. The single-nucleotide polymorphisms (SNPs) androgen receptor signaling genes influence effectiveness pathway inhibitors and deprivation therapy. Furthermore, SNPs located involved transport, drug metabolism, efflux pumps efficacy pharmacotherapy. Hence, provide basis for individualized pharmacotherapeutic PCa include hormonal therapy, chemotherapy (Docetaxel, Mitoxantrone, Cabazitaxel, Estramustine, etc.), radiotherapy. Here, we overview impact various evaluate current an emphasis early diagnosis treatment strategy PCa.

Language: Английский

---

Design, synthesis and biological evaluation of novel 2,4,6-trisubstituted quinazoline derivatives as potential antitumor agents

Medicinal Chemistry Research, Journal Year: 2023, Volume and Issue: 32(8), P. 1832 - 1850

Published: July 6, 2023

Language: Английский

---

Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy

Annals of Medicine, Journal Year: 2024, Volume and Issue: 57(1)

Published: Dec. 23, 2024

Background Increasing evidence indicates that cancer stem cells (CSCs) and stem-like form a special subpopulation of are ubiquitous in tumors. These exhibit similar characteristics to those normal tissues; moreover, they capable self-renewal differentiation, as well high tumorigenicity drug resistance. In prostate (PCa), it is difficult kill these using androgen signaling inhibitors chemotherapy drugs. Consequently, the residual (PCSCs) mediate tumor recurrence progression.

Language: Английский

---