Mitochondria: The metabolic switch of cellular oncogenic transformation

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2021, Volume and Issue: 1876(1), P. 188534 - 188534

Published: March 30, 2021

Language: Английский

---

The transcription factor PAX8 promotes angiogenesis in ovarian cancer through interaction with SOX17

Science Signaling, Journal Year: 2022, Volume and Issue: 15(728)

Published: April 5, 2022

PAX8 is a master transcription factor that essential during embryogenesis and promotes neoplastic growth. It expressed by the secretory cells lining female reproductive tract, its deletion development results in atresia of tract organs. Nearly all ovarian carcinomas express PAX8, knockdown apoptosis cancer cells. To explore role these tissues, we purified protein complex from nonmalignant fallopian tube high-grade serous carcinoma cell lines. We found was member large chromatin remodeling preferentially interacted with SOX17, another developmental factor. Depleting either or SOX17 altered expression factors involved angiogenesis functionally disrupted tubule capillary formation culture mouse models. promoted secretion angiogenic suppressing SERPINE1 , which encodes proteinase inhibitor anti ngiogenic effects. The findings reveal non–cell-autonomous function regulating cancer.

Language: Английский

---

Role of Mitochondrial Stress Response in Cancer Progression

Cells, Journal Year: 2022, Volume and Issue: 11(5), P. 771 - 771

Published: Feb. 23, 2022

Mitochondria are subcellular organelles that a hub for key biological processes, such as bioenergetic, biosynthetic, and signaling functions. implicated in all oncogenic from malignant transformation to metastasis resistance chemotherapeutics. The harsh tumor environment constantly exposes cancer cells cytotoxic stressors, nutrient starvation, low oxygen, oxidative stress. Excessive or prolonged exposure these stressors can cause irreversible mitochondrial damage, leading cell death. To survive hostile microenvironments perturb function, activate stress response maintain protein genome integrity. This adaptive mechanism, which is closely linked enables rapid adjustment survival environmental conditions encountered during dissemination, thereby promoting progression. In this review, we describe how the mitochondria contributes acquisition of typical traits highlight potential targeting an anti-cancer therapeutic strategy.

Language: Английский

---

Metabolic changes during prostate cancer development and progression

Journal of Cancer Research and Clinical Oncology, Journal Year: 2022, Volume and Issue: 149(5), P. 2259 - 2270

Published: Sept. 23, 2022

Abstract Metabolic reprogramming has been recognised as a hallmark in solid tumours. Malignant modification of the tumour’s bioenergetics provides energy for tumour growth and progression. Otto Warburg first reported these metabolic biochemical changes 1927. In prostate cancer (PCa) epithelial cells, metabolism also during development progress. These alterations are partly driven by androgen receptor, key regulator PCa development, progress, survival. contrast to other cells different entities, glycolytic sustains physiological citrate secretion normal prostatic epithelium. early stages PCa, is utilised power oxidative phosphorylation fuel lipogenesis, enabling advanced incurable castration-resistant shift towards choline, amino acid, fueling progression described. Therefore, even if not fully understood, altered may provide opportunities novel therapeutic strategies, especially stages. This review focuses on main differences PCa’s tumourigenesis highlighting glutamine’s role PCa.

Language: Английский

---

Emerging Hallmarks of Metabolic Reprogramming in Prostate Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 910 - 910

Published: Jan. 4, 2023

Prostate cancer (PCa) is the most common male malignancy and fifth leading cause of death in men worldwide. cells are characterized by a hybrid glycolytic/oxidative phosphorylation phenotype determined androgen receptor signaling. An increased lipogenesis cholesterogenesis have been described PCa cells. Many studies shown that enzymes involved these pathways overexpressed PCa. Glutamine becomes an essential amino acid for cells, its metabolism thought to become attractive therapeutic target. A crosstalk between stromal occurs tumor microenvironment because release different cytokines growth factors due changes extracellular matrix. deeper insight into metabolic may be obtained multi-omic approach integrating genomics, transcriptomics, metabolomics, lipidomics, radiomics data.

Language: Английский

---

Synchronous Interventions of Glucose and Mitochondrial Metabolisms for Antitumor Bioenergetic Therapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(29)

Published: April 22, 2023

Hydrogen sulfide (H2 S)-based mitochondrial bioenergetic intervention is an attractive therapeutic modality. However, its efficacy limited owing to metabolic plasticity, which allows tumors shift their phenotype between oxidative phosphorylation and glycolysis for energy compensation. To overcome this flexibility, a glycopolymer containing caged H2 S hydrogen peroxide O2 ) dual-donor (1-thio-β-D-glucose [thioglucose]) synthesized wrap glucose oxidase (GOx) complete depletion of tumorigenic sources. The loaded GOx catalyzes the glutathione-activated thioglucose generate cytotoxic S/H2 , further induces synergistic defects in function by suppressing cytochrome c expression damaging membrane potential. also blocks depleting endogenous glucose. This synchronous strategy exhibits good anticancer performance, broadening horizon antitumor therapy.

Language: Английский

---

Preclinical models of prostate cancer — modelling androgen dependency and castration resistance in vitro, ex vivo and in vivo

Nature Reviews Urology, Journal Year: 2023, Volume and Issue: 20(8), P. 480 - 493

Published: Feb. 14, 2023

Language: Английский

---

Metabolic adaptations in prostate cancer

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 131(8), P. 1250 - 1262

Published: July 5, 2024

Prostate cancer is one of the most commonly diagnosed cancers in men and a major cause cancer-related deaths worldwide. Among molecular processes that contribute to this disease, weight metabolism has been placed under limelight recent years. Tumours exhibit metabolic adaptations comply with their biosynthetic needs. However, metabolites also play an important role supporting cell survival challenging environments or remodelling tumour microenvironment, thus being recognized as hallmark cancer. uniquely driven by androgen receptor signalling, knowledge influenced paths research. This review provides comprehensive perspective on support prostate progression beyond particular focus intrinsic extrinsic pathways.

Language: Английский

---

Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 12, 2024

Abstract Prostate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate 95% advanced stages. A myriad molecular events and mutations, including accumulation oncometabolites, underpin genesis progression this cancer type. Despite growing research demonstrating pivotal role oncometabolites supporting various cancers, prostate root causes their accumulation, especially absence enzymatic remain elusive. Consequently, identifying a tangible therapeutic target poses formidable challenge. In review, we aim to delve deeper into implications oncometabolite cancer. We center our focus on consequential epigenetic alterations impacts stem cells, with ultimate goal outlining novel strategies. Graphical

Language: Английский

---

The estrogen signaling pathway reprograms prostate cancer cell metabolism and supports proliferation and disease progression

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(11)

Published: April 16, 2024

Just as the androgen receptor (AR), estrogen α (ERα) is expressed in prostate and thought to influence cancer (PCa) biology. Yet, incomplete understanding of ERα functions PCa hinders our ability fully comprehend its clinical relevance restricts repurposing estrogen-targeted therapies for treatment this disease. Using two human tissue microarray cohorts, we first demonstrated that nuclear expression was heterogeneous among patients, being only detected half tumors. Positive levels were correlated with disease recurrence, progression metastatic PCa, patient survival. vitro vivo models normal bulk single-cell RNA-Seq analyses revealed estrogens partially mimic transcriptional response induce specific biological pathways linked proliferation metabolism. Bioenergetic flux assays metabolomics confirmed regulation metabolism by estrogens, supporting proliferation. cell lines patient-derived organoids, selective modulators, a pure anti-estrogen, genetic approaches impaired growth an ERα-dependent manner. Overall, study that, when expressed, functionally reprograms metabolism, associated progression, could be targeted therapeutic purposes.

Language: Английский

---