Regulation of lipid metabolism by E3 ubiquitin ligases in lipid-associated metabolic diseases DOI Creative Commons
Yuanming Zou, Ying Zhang, Mohan Li

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 265, P. 130961 - 130961

Published: March 18, 2024

Previous studies have progressively elucidated the involvement of E3 ubiquitin (Ub) ligases in regulating lipid metabolism. Ubiquitination, facilitated by Ub ligases, modifies critical enzymes metabolism, enabling them to respond specific signals. In this review, we aim present a comprehensive analysis role which includes synthesis and lipolysis, their influence on cellular homeostasis through modulation uptake efflux. Furthermore, it explores how ubiquitination process governs degradation or activation pivotal enzymes, thereby metabolism at transcriptional level. Perturbations been implicated various diseases, including hepatic disorders, atherosclerosis, diabetes, cancer. Therefore, review focuses association between lipid-related highlighting critically involved catabolism, regulators, translocators, transporters. Overall, aims identify gaps current knowledge, highlight areas requiring further research, offer potential targeted therapeutic approaches, provide outlook clinical conditions associated with metabolic diseases.

Language: Английский

CPT1A mediates the succinylation of SP5 which activates transcription of PDPK1 to promote the viability and glycolysis of prostate cancer cells DOI Creative Commons
Shufeng Liu,

Xiaoguang Chen,

Liqi Zhang

et al.

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 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.

Language: Английский

Citations

7
Survival mechanisms of circulating tumor cells and their implications for cancer treatment DOI
Shuang Zhou, Huanji Xu,

Yichun Duan

et al.

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Language: Английский

Citations

6
Circ_0007534 promotes cholangiocarcinoma stemness and resistance to anoikis through DDX3X-mediated positive feedback regulation of parental gene DDX42 DOI
Sidi Liu, Canghai Guan,

Xiangjun Sha

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 118, P. 111141 - 111141

Published: March 16, 2024

Language: Английский

Citations

4
APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition DOI Creative Commons
Huihui Zhao, Xinxin Cheng, Liping Yan

et al.

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

Published: May 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

Language: Английский

Citations

4
GDF15 enhances anoikis resistance and metastasis of gastric cancer through protective autophagy DOI Creative Commons
Xinyu Gao, Zhongwei Zhang,

Qinyi Li

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 124, P. 111457 - 111457

Published: Oct. 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.

Language: Английский

Citations

4
Metabolic reprogramming and immunological changes in the microenvironment of esophageal cancer: future directions and prospects DOI Creative Commons
Zhixun Guo, Jiali Ma, Jinqiu Zhang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 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.

Language: Английский

Citations

0
An untargeted metabolomic analysis of acute AFB1 treatment in liver, breast, and lung cells DOI Creative Commons
He Cao,

Sabrina Molina,

Susan Sumner

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0313159 - e0313159

Published: Jan. 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.

Language: Английский

Citations

0
Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment DOI Creative Commons
Mengting Wan,

Shuaikang Pan,

Benjie Shan

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 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.

Language: Английский

Citations

0
Anoikis Resistance in Cancer: Mechanisms, Therapeutic Strategies, Potential Targets, and Models for Enhanced Understanding DOI
Pallab Shaw, Arpan Dey Bhowmik, Mohan Shankar Gopinatha Pillai

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217750 - 217750

Published: April 1, 2025

Language: Английский

Citations

0
FOXM1 boosts glycolysis by upregulating SQLE to inhibit anoikis in breast cancer cells DOI Creative Commons

Mei Xu,

Guoyuan Pan, Qian Zhang

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2025, Volume and Issue: 151(5)

Published: May 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.

Language: Английский

Citations

0