CPT1A mediates radiation sensitivity in colorectal cancer DOI Creative Commons
Zhenhui Chen, Lu Yu, Zhihao Zheng

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Ноя. 28, 2024

The prevalence and mortality rates of colorectal cancer (CRC) are increasing worldwide. Radiation resistance hinders radiotherapy, a standard treatment for advanced CRC, leading to local recurrence metastasis. Elucidating the molecular mechanisms underlying radioresistance in CRC is critical enhance therapeutic efficacy patient outcomes. Bioinformatic analysis tumour tissue examination were conducted investigate CPT1A mRNA protein levels their correlation with radiotherapy efficacy. Furthermore, lentiviral overexpression CRISPR/Cas9 vectors, along vitro vivo radiation experiments, used explore effect on radiosensitivity. Additionally, transcriptomic sequencing, biology bioinformatic analyses employed elucidate by which regulates was significantly downregulated negatively correlated responsiveness neoadjuvant radiotherapy. Functional studies suggested that mediates radiosensitivity, influencing reactive oxygen species (ROS) scavenging DNA damage response. Transcriptomic highlighted involvement peroxisomal pathway. Mechanistic exploration revealed downregulates FOXM1-SOD1/SOD2/CAT axis, moderating cellular ROS after irradiation enhancing downregulation contributes augmenting FOXM1-mediated antioxidant Thus, potential biomarker radiosensitivity novel target overcoming radioresistance, offering future direction

Язык: Английский

Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage DOI Creative Commons
Shan Tian, Ruixue Li, Jiao Li

и другие.

Environment International, Год журнала: 2025, Номер 195, С. 109258 - 109258

Опубликована: Янв. 1, 2025

Nanoplastics (NPs) have attracted widespread attention owing to their presence in the body. Recent studies highlighted detrimental effects of NPs on digestive tract. However, no reported an association between exposure and colitis-associated cancer (CAC). An azoxymethane/dextran sodium sulfate-induced CAC model was used, polystyrene nanoparticles (PS-NPs) were selected for long-term exposure. Non-targeted metabolomics 16S rRNA sequencing used detect changes colonic metabolites gut microbes following PS-NPs A lipopolysaccharide (LPS)-treated cell (Caco-2) exposed investigate underlying molecular mechanism. Compared normal control group, mice group exhibited more tumor nodes reactive oxygen species (ROS), higher expression pan-CK Ki-67, severe DNA damage. revealed that altered abundance Allobaculum Lactobacillus, whereas metabolic analysis showed most significant enriched mostly fatty acid metabolism. Experiments LPS intervened Caco-2 cells led lipid peroxidation, oxidative stress, damage Caco-2. Exposure activated phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) signaling pathway both AOM/DSS mouse cellular model. Key proteins involved metabolism downregulated PS-NPs. The significantly inhibited by activation fenofibrate. disturbed induced via PI3K/AKT/mTOR promote progression. Inhibition is a therapeutic controlling PS-NP-induced CAC. Our study provides important reference prevention treatment from perspective environment enhances awareness necessity plastic control.

Язык: Английский

Процитировано

3
ALKBH5-mediated upregulation of CPT1A promotes macrophage fatty acid metabolism and M2 macrophage polarization, facilitating malignant progression of colorectal cancer DOI Creative Commons
Mingming Sun, Yinzi Yue, Xiaopeng Wang

и другие.

Experimental Cell Research, Год журнала: 2024, Номер 437(1), С. 113994 - 113994

Опубликована: Март 12, 2024

m6A modification has been studied in tumors, but its role host anti-tumor immune response and TAMs polarization remains unclear. The fatty acid oxidation (FAO) process of is also attracting attention. A co-culture model colorectal cancer (CRC) cells macrophages was used to simulate the tumor microenvironment. Expression changes demethylase genes FTO ALKBH5 were screened. further investigated. Gain-of-function experiments conducted study ALKBH5's effects on macrophage M2 polarization, CRC cell viability, proliferation, migration, more. Me-RIP Actinomycin D assays performed influence CPT1A, FAO rate-limiting enzyme. AMP, ADP, ATP content detection, OCR measurement, ECAR measurement explore impact level. Rescue validated mechanistic malignant development. In co-culture, enhance suppress macrophages. selected as gene for investigation. mediates CPT1A upregulation by removing modification, promoting facilitating These findings indicate that enhances metabolism upregulating thereby

Язык: Английский

Процитировано

11
Targeting fatty acid oxidation: A potential strategy for treating gastrointestinal tumors DOI Open Access

Yaxi Zheng,

Zhengchen Jiang,

Li Yuan

и другие.

International Journal of Cancer, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Gastrointestinal cancers including esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), and colorectal (CRC) are common highly lethal types of worldwide. Metabolic reprogramming plays a critical role in progression involves metabolic processes such as glucose lipid metabolism. Fatty acid oxidation (FAO) has profound impact on cancer, with many genes cytokines influencing initiation, development, metastasis, resistance by regulating FAO. Additionally, FAO further promotes affecting the tumor microenvironment (TME). The gastrointestinal garnered increasing attention, related anticancer drugs currently being developed.

Язык: Английский

Процитировано

1
SLC31A1 promotes chemoresistance through inducing CPT1A-mediated fatty acid oxidation in ER-positive breast cancer DOI Creative Commons
Xudong Li,

Jingjing Ge,

Mengdi Wan

и другие.

Neoplasia, Год журнала: 2025, Номер 61, С. 101125 - 101125

Опубликована: Фев. 3, 2025

Язык: Английский

Процитировано

1
Metabolic crossroads: unravelling immune cell dynamics in gastrointestinal cancer drug resistance DOI Open Access

C. Raman Suri,

Babita Pande,

Lakkakula Suhasini Sahithi

и другие.

Cancer Drug Resistance, Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance gastrointestinal cancers (GI), particularly through pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth reshape TME, creating conditions such as nutrient depletion, hypoxia, acidity that impair antitumor immune responses. Immune TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes promote progression reduce efficacy therapies. The competition for essential nutrients, glucose, between cancer compromises functions effector cells, T cells. Additionally, by-products like lactate kynurenine further suppress activity populations, including regulatory M2 macrophages. Targeting glycolysis presents new opportunities overcome improve therapeutic outcomes GI cancers. Modulating these key has potential reinvigorate exhausted shift toward phenotypes, enhance effectiveness immunotherapies other treatments. Future strategies will require continued research into metabolism, development novel inhibitors, clinical trials evaluating combination Identifying validating biomarkers be crucial patient stratification treatment monitoring. Insights may have broader implications across multiple types, offering avenues improving treatment.

Язык: Английский

Процитировано

1
Metabolic reprogramming in lung cancer and its clinical implication DOI Creative Commons
Qingqiu Huang, Lisha Fan, Ming Gong

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Дек. 18, 2024

Lung cancer has posed a significant challenge to global health, and related study been hot topic in oncology. This article focuses on metabolic reprogramming of lung cells, process adapt energy demands biosynthetic needs, supporting the proliferation development tumor cells. In this study, latest studies metabolism were reviewed, including impact products enzymes occurrence cancer, as well progress field treatment targeting relevant pathways. provides some promising potential directions into exploring helps researchers better understand cancer.

Язык: Английский

Процитировано

3
CPT1A mediates succinylation of LDHA at K318 site promoteing metabolic reprogramming in NK/T-cell lymphoma nasal type DOI Creative Commons
Hao Tian,

Ge Yi,

Jianjun Yu

и другие.

Cell Biology and Toxicology, Год журнала: 2025, Номер 41(1)

Опубликована: Фев. 11, 2025

Carnitine palmitoyltransferase 1A (CPT1A), a succinylating enzyme, is highly expressed in various malignant tumors and promotes tumor progression. Succinylation posttranslational modification that has been reported diseases, but its role NK/T-Cell lymphoma nasal type (ENKTL-NT) remains underexplored. In this study, bioinformatics analysis showed glycolytic major metabolic pathway ENKTL-NT as the expression of many related kinases are increased. CPT1A probably mediates process, indicated by GO-enrichment analysis. Studies was upregulated tissues, high associated with poor prognosis ENKTL-NT. promoted proliferation, colony formation, invasion process cells suppresses apoptosis. Mechanistically, succinylation LDHA at lysine 318 (K318), which increase protein stability final level LDHA. Both knockdown mutation (K318R) abolished cancer-promoting effects all, study reveals mechanism underlying via inducing reprogramming These findings might provide potential targets for diagnosis or therapy

Язык: Английский

Процитировано

0
International Union of Basic and Clinical Pharmacology: Fundamental Insights and Clinical Relevance Regarding the Carnitine Palmitoyltransferase Family of Enzymes DOI Creative Commons
Rosalía Rodríguez‐Rodríguez, Miguel Baena, Sebastián Zagmutt

и другие.

Pharmacological Reviews, Год журнала: 2025, Номер unknown, С. 100051 - 100051

Опубликована: Фев. 1, 2025

The carnitine palmitoyltransferases (CPTs) play a key role in controlling the oxidation of long-chain fatty acids and are potential therapeutic targets for diseases with strong metabolic component, such as obesity, diabetes, cancer. Four distinct proteins CPT1A, CPT1B, CPT1C, CPT2, differing tissue expression catalytic activity. CPT1s finely regulated by malonyl-CoA, metabolite whose intracellular levels reflect cell's nutritional state. Although CPT1C does not exhibit significant activity, it is capable modulating functioning other neuronal proteins. Structurally, all CPTs share Y-shaped tunnel that allows entry 2 substrates accommodation acyl group hydrophobic pocket. Several molecules targeting these enzymes have been described, some showing normalizing blood glucose diabetic patients, others that, through central mechanism, anorexigenic enhance energy expenditure. However, given critical roles certain tissues, heart, liver, brain, essential to fully understand differences between various isoforms. We analyze detail structure proteins, their cellular physiological functions, also describe drugs identified date having inhibitory or activating capabilities This knowledge will support design new specific each isoform, development nanomedicines can selectively target particular tissues cells. SIGNIFICANCE STATEMENT: Carnitine palmitoyltransferase (CPT) gatekeepers acid oxidation, great pharmacological treat like In recent years, progress has made understanding 3-dimensional pathophysiological functions. A deeper CPT family members enable selective approaches fewer side effects.

Язык: Английский

Процитировано

0
Proteomics-driven discovery of LCAT as a novel biomarker for liver metastasis in colorectal cancer DOI Creative Commons
Yuyao Wang, Zhan Yang,

Ziqun Li

и другие.

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Март 15, 2025

This study aimed to identify molecular markers that influence liver metastasis in colorectal cancer (CRC) and assess their clinical relevance. Proteomic analysis compared differential protein expression between CRC patients with (CRLM) those without (CRNLM). Bioinformatics survival analyses identified key proteins validated them using the TCGA database for significance. Clinical pathological data, along tissue samples from our center, were used create microarrays immunohistochemistry. Logistic regression assessed odds ratios (OR) linked post-CRC surgery. Stable LCAT knockdown overexpression cell lines constructed, Transwell assays impact on migration. Nile red staining of these cells effect lipid metabolism cells. 383 differentially expressed CRLM CRNLM groups (212 upregulated, 171 downregulated). Enrichment steroid alcohol metabolism, inflammation, lipoproteins, HDL particles, pathways cholesterol retinol metabolism. Lecithin acyltransferase (LCAT), an important enzyme this process, showed higher tissues, increased poorer 5-year OS, DSS, PFI. also tumor stage. Among 119 CRC, preoperative complications, staging, scores differed significantly within 3 years post-surgery. postoperative CEA levels independent risk factors (LCAT OR, 10.221; P = 0.002; 1.296; 0.014). Western blotting confirmed tissues metastasis. enhanced migratory ability, while inhibited it. revealed droplet accumulation LCAT-overexpressing cells, which was reduced by knockdown. LCAT, is involved factor following surgery, suggesting its potential as a therapeutic target.

Язык: Английский

Процитировано

0
The solid tumor microenvironment and related targeting strategies: a concise review DOI Creative Commons
Yingliang Wang, Huimin Zhou, Shuguang Ju

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 26, 2025

The malignant tumor is a serious disease threatening human life. Increasing studies have confirmed that the microenvironment (TME) composed of variety complex components precisely regulate interaction cells with other components, allowing to continue proliferate, resist apoptosis, evade immune surveillance and clearance, metastasis. However, characteristics each component their interrelationships remain be deeply understood. To target TME, it necessary understand role various TME in growth search for potential therapeutic targets. Herein, we innovatively classify into physical (such as oxygen, pH, etc.), mechanical extracellular matrix, blood vessels, metabolic glucose, lipids, inflammatory microenvironment. We introduce concise but comprehensive classification TME; depict summarize existing methods detecting highlight current strategies targets discuss challenges presenting its clinical applications; provide our prospect on future research direction benefits TME.

Язык: Английский

Процитировано

0