CPT1A mediates the succinylation of SP5 which activates transcription of PDPK1 to promote the viability and glycolysis of prostate cancer cells

Cancer Biology & Therapy, Год журнала: 2024, Номер 25(1)

Опубликована: Март 17, 2024

Succinylation modification involves in the progression of human cancers. The present study aimed to investigate role CPT1A, which is a succinyltransferase prostate cancer (PCa). CCK-8 was used detect cell viability. Seahorse performed evaluate glycolysis. Luciferase assay transcriptional regulation. ChIP assess binding between factors with promoters. Co-IP proteins. We found that CPT1A highly expressed PCa tissues and lines. Silencing inhibited viability glycolysis cells. Mechanistically, promoted succinylation SP5, strengthened SP5 promoter PDPK1. activated PDPK1 transcription AKT/mTOR signal pathway. These findings might provide novel targets for diagnosis or therapy cancer.

Язык: Английский

---

Survival mechanisms of circulating tumor cells and their implications for cancer treatment

Cancer and Metastasis Reviews, Год журнала: 2024, Номер unknown

Опубликована: Март 4, 2024

Язык: Английский

---

Circ_0007534 promotes cholangiocarcinoma stemness and resistance to anoikis through DDX3X-mediated positive feedback regulation of parental gene DDX42

Cellular Signalling, Год журнала: 2024, Номер 118, С. 111141 - 111141

Опубликована: Март 16, 2024

Язык: Английский

---

APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Май 23, 2024

Abstract Background In addition to functioning as a precise monitoring mechanism in cell cycle, the anaphase-promoting complex/cyclosome (APC/C) is reported be involved regulating multiple metabolic processes by facilitating ubiquitin-mediated degradation of key enzymes. Fatty acid oxidation pathway utilized tumor cells that crucial for malignant progression; however, its association with APC/C remains explored. Methods Cell cycle synchronization, immunoblotting, and propidium iodide staining were performed investigate carnitine palmitoyltransferase 1 C (CPT1C) expression manner. Proximity ligation assay co-immunoprecipitation detect interactions between CPT1C APC/C. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium, inner salt (MTS) assays, cell-scratch transwell assays xenograft transplantation role progression vitro vivo. Immunohistochemistry was on tissue microarray evaluate levels explore potential clinical value. Results We identified novel substrate. protein exhibited cycle-dependent fluctuations, peaking at G1/S boundary. Elevated accelerated transition, proliferation Furthermore, enhanced fatty utilization, upregulated ATP levels, decreased reactive oxygen species thereby favoring survival harsh environment. Clinically, high correlated poor patients esophageal squamous carcinoma. Conclusions Overall, our results revealed interplay utilization machinery cells. Additionally, promoted augmenting cellular preserving redox homeostasis, particularly under stress. Therefore, could an independent prognostic indicator

Язык: Английский

---

GDF15 enhances anoikis resistance and metastasis of gastric cancer through protective autophagy

Cellular Signalling, Год журнала: 2024, Номер 124, С. 111457 - 111457

Опубликована: Окт. 9, 2024

Distant metastasis is a prevalent cause of mortality in gastric cancer (GC) patients. Anoikis, process that induces cell death when cells get detached from the extracellular matrix (ECM), acts as barrier to tumor metastasis. To survive circulatory system and metastasize, must acquire anoikis resistance. It crucial identify molecular processes resistance GC since this might lead discovery novel treatment targets improve long-term survival In study, we employed quantitative proteomics growth differentiation factor 15 (GDF15) key We found GDF15 enhances protective autophagy, thereby promoting cells. Furthermore, through DNA pull down assay, activating transcription 2 (ATF2) was be critical regulator expression, acting transcriptional activator GDF15. Collectively, these discoveries indicate ATF2 have great potential target candidates for developing therapeutic strategies address GC.

Язык: Английский

---

Metabolic reprogramming and immunological changes in the microenvironment of esophageal cancer: future directions and prospects

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 24, 2025

Background Esophageal cancer (EC) is the seventh-most prevalent worldwide and a significant contributor to cancer-related mortality. Metabolic reprogramming in tumors frequently coincides with aberrant immune function alterations, extensive research has demonstrated that perturbations energy metabolism within tumor microenvironment influence occurrence progression of esophageal cancer. Current treatment modalities for primarily include encompass chemotherapy limited array targeted therapies, which are hampered by toxicity drug resistance issues. Immunotherapy, particularly checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathway, exhibited promising results; however, substantial proportion patients remain unresponsive. The optimization these immunotherapies requires further investigation. Mounting evidence underscores importance modulating metabolic traits (TME) augment anti-tumor immunotherapy. Methods We selected relevant studies on cells based our searches MEDLINE PubMed, focusing screening experimental articles reviews related glucose metabolism, amino acid lipid as well their interactions cells, published last five years. analyzed discussed studies, while also expressing own insights opinions. Results A total 137 were included review: 21 focused cancer, 33 delved into immunology, 30 introduced responses, 17 relationship between both cells. Conclusion This article delves alterations TME EC, systematically synthesizes characteristics TME, dissects consolidates harnesses pertinent immunotherapy targets, goal enhancing thereby offering development novel therapeutic strategies.

Язык: Английский

---

An untargeted metabolomic analysis of acute AFB1 treatment in liver, breast, and lung cells

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0313159 - e0313159

Опубликована: Янв. 30, 2025

Aflatoxin B1 (AFB1) is a class 1 carcinogen and mycotoxin known to contribute the development of hepatocellular carcinoma (HCC), growth impairment, altered immune system modulation, malnutrition. AFB1 synthesized by Aspergillus flavus widely contaminate foodstuffs, particularly maize, wheat, groundnuts. The mechanism in which causes genetic mutations has been well studied, however its metabolomic effects remained largely unknown. A better understanding how disrupts metabolism would provide insight into this leads carcinogenesis, and/or immunomodulation, may reveal potential targets for pharmacological or nutritional interventions protect against these effects. current study evaluated various doses (2.5 μM, 5 10uM) treatment HepG2 (liver), MDA-MB-231 (breast), A549 (lung) cells. Treated control cells’ profiles were via ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Univariate multivariate analyses revealed significant alterations metabolite concentrations from each dose cell type. Pathway analysis was then used understand broader biochemical functions affected pathway perturbations lipid metabolism, carnitine synthesis, catecholamine biosynthesis, purine spermidine spermine biosynthesis. Analysis cells found greater emphasis on amino acids along with synthesis-related pathways, Finally, treated plasma membrane-related pathways (phosphatidylcholine synthesis alpha linolenic acid linoleic metabolism), be most affected. These highlighted should targeted future investigations evaluate their mitigating preventing negative health associated exposure.

Язык: Английский

---

Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 3, 2025

Aberrant lipid metabolism is a well-recognized hallmark of cancer. Notably, breast cancer (BC) arises from lipid-rich microenvironment and depends significantly on metabolic reprogramming to fulfill its developmental requirements. In this review, we revisit the pivotal role in BC, underscoring impact progression tumor microenvironment. Firstly, delineate overall landscape highlighting roles patient prognosis. Given that lipids can also act as signaling molecules, next describe exchanges between BC cells other cellular components Additionally, summarize therapeutic potential targeting aspects processes, lipid-related transcription factors immunotherapy BC. Finally, discuss possibilities problems associated with clinical applications lipid‑targeted therapy propose new research directions advances spatiotemporal multi-omics.

Язык: Английский

---

Anoikis Resistance in Cancer: Mechanisms, Therapeutic Strategies, Potential Targets, and Models for Enhanced Understanding

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217750 - 217750

Опубликована: Апрель 1, 2025

Язык: Английский

---

FOXM1 boosts glycolysis by upregulating SQLE to inhibit anoikis in breast cancer cells

Journal of Cancer Research and Clinical Oncology, Год журнала: 2025, Номер 151(5)

Опубликована: Май 13, 2025

Resisting anoikis is a prerequisite for cancer to spread and invade major cause of cancer-related deaths. Yet, the intricate mechanisms how cells evade remain largely unknown. There significant need explore these play out in breast (BC). Bioinformatics analysis revealed expression levels SQLE FOXM1 BC tissue, along with their correlation. The enrichment pathways were also explored. qPCR detected cells. CCK-8 assessed cell viability, while flow cytometry measured anoikis. Western blot was employed examine protein key genes glycolytic metabolism apoptosis-related proteins. Extracellular acidification rate quantified, corresponding kits evaluated glucose consumption, lactate production, adenosine triphosphate Dual-luciferase reporter assays chromatin immunoprecipitation tests unveiled binding relationship between SQLE. found be highly expressed enriched associated glycolysis. curbed via aerobic glycolysis pathway. direct positive correlation expression. Recovery experiments substantiated that targeted suppress upregulates SQLE, which turn mediates BC. FOXM1/SQLE axis promising therapeutic target treatment.

Язык: Английский

---