Inhibition of TFAM-Mediated Mitophagy by Oroxylin A Restored Sorafenib Sensitivity Under Hypoxia Conditions in HepG2 Cells DOI Creative Commons

Shufan Ji,

Xuefen Xu, Yujia Li

и другие.

Pharmaceuticals, Год журнала: 2024, Номер 17(12), С. 1727 - 1727

Опубликована: Дек. 20, 2024

Background: Liver cancer treatment encounters considerable therapeutic challenges, especially because hypoxic microenvironments markedly reduce sensitivity to chemotherapeutic agents. TFAM (mitochondrial transcription factor A) plays a crucial role in maintaining mitochondrial function. Oroxylin A (OA), flavonoid with potential properties, demonstrated prospects treatment. However, the mechanism of sensitizing effect OA on cells has not been elucidated. Methods: MTT assays were utilized evaluate hypoxia-induced resistance model. Plate colony formation assays, TEM, and JC-1 staining used examine effects siTFAM proliferation damage HepG2 cells. Cox8-EGFP-mCherry plasmid transfection, LysoTracker MitoTracker colocalization analysis, WB conducted influence mitophagy. The p53 ubiquitination levels was investigated by Co-IP CHX chase assay. mouse xenograft tumor model assess vivo. Results: significantly improved inhibitory sorafenib inhibiting mitophagy vitro vivo models. Notably, molecular docking thermal shift indicated clear binding TFAM. Further research revealed that suppressed acetylation promoted its degradation downregulating expression, which ultimately inhibited hypoxia. Conclusions: enhance efficacy for liver cancer, may be one targets.

Язык: Английский

Therapeutic advances of targeting receptor tyrosine kinases in cancer DOI Creative Commons
Ciprian Tomuleasa, Adrian Bogdan Țigu, Raluca Munteanu

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 14, 2024

Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.

Язык: Английский

Процитировано

24
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

и другие.

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Язык: Английский

Процитировано

16
Renal cancer: signaling pathways and advances in targeted therapies DOI Creative Commons
Aimin Jiang, Jinxin Li,

Ziwei He

и другие.

MedComm, Год журнала: 2024, Номер 5(8)

Опубликована: Авг. 1, 2024

Abstract Renal cancer is a highlyheterogeneous malignancy characterized by rising global incidence and mortalityrates. The complex interplay dysregulation of multiple signaling pathways,including von Hippel–Lindau ( VHL )/hypoxia‐inducible factor HIF ), phosphoinositide 3‐kinase PI3K )/protein kinase B AKT )/mammalian target rapamycin mTOR Hippo–yes‐associated protein YAP Wnt/ß‐catenin, cyclic adenosine monophosphate cAMP hepatocyte growth HGF )/ c‐Met , contribute to theinitiation progression renal cancer. Although surgical resection thestandard treatment for localized cancer, recurrence metastasiscontinue pose significant challenges. Advanced associatedwith poor prognosis, current therapies, such as targeted agents andimmunotherapies, have limitations. This review presents comprehensiveoverview the molecular mechanisms underlying aberrant pathways inrenal emphasizing their intricate crosstalk synergisticinteractions. We discuss recent advancements in includingtyrosine inhibitors, immunotherapies, checkpoint inhibitors.Moreover, we underscore importance multiomics approaches networkanalysis elucidating regulatory networks governing cancerpathogenesis. By integrating cutting‐edge research clinical insights, this contributesto development innovative diagnostic therapeutic strategies, whichhave potential improve risk stratification, precision medicine, andultimately, patient outcomes

Язык: Английский

Процитировано

5
Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study DOI Creative Commons

Bai‐Horng Su,

Zhiyao Fan, Jianguo Wu

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 25, 2025

Previous studies have found that dyslipidemia is a risk factor for pancreatic cancer (PC), and lipid-lowering drugs may reduce the of PC. However, it not clear whether causes The Mendelian randomization (MR) study aimed to investigate causal role lipid traits in assess potential impact drug targets on cancer. Genetic variants associated with genes encoding were extracted from Global Lipids Genetics Consortium genome-wide association (GWAS). Summary statistics PC obtained an independent GWAS datasets. Colocalization analyses performed validate robustness results. No significant effect was found. mimicry lipoprotein lipase (LPL) potentially risks. Significant MR associations observed discovery dataset (OR 1.64 [95% CI 1.24–2.16], p = 4.48*10–4) one dataset. finding verified replication Our findings do support as Among targets, LPL target

Язык: Английский

Процитировано

0
Immunomodulation on tumor immune microenvironment in acquired targeted therapy resistance and implication for immunotherapy resistance DOI

Ming-Yu Chou,

Muh‐Hwa Yang

Translational Oncology, Год журнала: 2025, Номер 54, С. 102353 - 102353

Опубликована: Март 8, 2025

Язык: Английский

Процитировано

0
Eleven inflammation-related genes risk signature model predicts prognosis of patients with breast cancer DOI Open Access
Huanhuan Hu,

Shenglong Yuan,

Yuqi Fu

и другие.

Translational Cancer Research, Год журнала: 2024, Номер 13(7), С. 3652 - 3667

Опубликована: Июль 1, 2024

Changes in gene expression are associated with malignancy. Analysis of data could be used to reveal cancer subtypes, key molecular drivers, and prognostic characteristics predict susceptibility, treatment response, mortality. It has been reported that inflammation plays an important role the occurrence development tumors. Our aim was establish a risk signature model breast inflammation-related genes (IRGs) evaluate their survival prognosis.

Язык: Английский

Процитировано

2
TRIB3 knockdown increases the sensitivity of clear cell renal cell carcinoma to sunitinib by inducing ferroptosis DOI
Zixuan Chen, Xing Jia, Zhou Wang

и другие.

Cellular Signalling, Год журнала: 2024, Номер 124, С. 111421 - 111421

Опубликована: Сен. 17, 2024

Язык: Английский

Процитировано

2
TYROBP promotes the spread of pancreatic cancer by causing M2 TAM polarization DOI
Dingwen Zhong, Yonghui Liao, Wenhui Chen

и другие.

Journal of Gastroenterology and Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

Abstract Background and Aim M2‐polarized tumor‐associated macrophages (M2 TAMs) are known to promote cancer progression, exosomes crucial mediators of communication within the tumor microenvironment (TME). However, specific role derived from M2 TAMs in pancreatic (PC) progression remains poorly understood. Tyrosine kinase binding protein (TYROBP, also as DAP12 for DNAX activating protein‐12) is a transmembrane signal transduction polypeptide that interacts with immune cell receptors, influencing cellular functions via pathways. TYROBP prominently found exosomes, facilitating its transfer PC cells suggesting potential pathogenesis. Methods This study initially confirmed presence exosomes. The impact on proliferation, apoptosis, migration, invasion was investigated. Special attention given TYROBP's influence metastasis underlying mechanisms, focusing particularly CD44/AKT/ERK signaling pathway. Results expression did not significantly affect proliferation or apoptosis but demonstrated notable inhibitory effect migration invasion, which mediated through Both vivo vitro experiments consistently showed enhanced metastasis. Conclusions elucidates plays direct promoting association polarization. Therefore, represents novel therapeutic target interventions aimed at combatting progression.

Язык: Английский

Процитировано

1
Recent advances in the treatment of non-small cell lung cancer with MET inhibitors DOI Creative Commons
Dongna Zhang, Wenying Zhang, He Liu

и другие.

Frontiers in Chemistry, Год журнала: 2024, Номер 12

Опубликована: Дек. 10, 2024

Recently, research into the oncogenic driver genes associated with non-small cell lung cancer (NSCLC) has advanced significantly, leading to development and clinical application of an increasing number approved therapeutic agents. Among these, small molecule inhibitors that target mesenchymal-epithelial transition (MET) have demonstrated successful in settings. Currently, three categories MET inhibitors, characterized by distinct binding patterns kinase region, been developed: types Ia/Ib, II, III. This review thoroughly examines MET’s structure its crucial role NSCLC initiation progression, explores discovery strategies for discusses advancements understanding resistance mechanisms. These insights are anticipated enhance a new generation high efficiency, selectivity, low toxicity, thereby offering additional alternatives patients diagnosed NSCLC.

Язык: Английский

Процитировано

1
Roles of deubiquitinases in urologic cancers (Review) DOI Open Access
Liangpei Wu, Jiahui Wang, Linjiang Chai

и другие.

Oncology Letters, Год журнала: 2024, Номер 28(6)

Опубликована: Окт. 14, 2024

Human health is endangered by the occurrence and progression of urological cancers, including renal cell carcinoma, prostate cancer bladder cancer, which are usually associated with activation oncogenic factors inhibition suppressors. The primary mechanism for protein breakdown in cells ubiquitin‑proteasome system, whilst deubiquitinases contribute to reversal this process. However, both important homeostasis. Deubiquitination may also be involved control cycle, proliferation apoptosis, dysregulated deubiquitination malignant transformation, invasion metastasis urologic malignancies. Therefore, a comprehensive summary mechanisms underlying cancers provide novel strategies insights diagnosis treatment. present review aimed methodically clarify role deubiquitinating enzymes urinary system as well their prospective application prospects clinical

Язык: Английский

Процитировано

0