Focal adhesion kinase and its epigenetic interactors as diagnostic and therapeutic hints for pediatric hepatoblastoma DOI Creative Commons
Maria Rita Braghini, Cristiano De Stefanis, Francesca Tiano

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 14, 2024

Background Hepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite progress in HB treatment, investigating pathomechanisms to optimize stratification and therapies remains a focal point improve outcome for high-risk patients. Methods Here, we pointed explore impact of these mechanisms HB. An observational study was performed on liver samples from cohort 17 patients with diagnosis two normal samples. The vitro experiments were executed Huh6 human cell line treated FAK inhibitor TAE226. Results Our results highlight significant up-regulation mRNA protein expression livers respect livers. increased total Tyr397 phosphorylated (pTyr397FAK) significantly correlated some epigenetic regulators histone H3 methylation acetylation. Of note, pTyr397FAK, N-methyltransferase enzyme (EZH2) tri-methylation H3K27 residue tumor size alpha-fetoprotein (AFP) levels. Finally, TAE226 caused reduction regulators, AFP , EPCAM OCT4 SOX2 association anti-proliferative pro-apoptotic effects cells. Conclusion suggest role that requires further investigations mainly focused exploration its effective diagnostic therapeutic translatability.

Language: Английский

Advances and challenges in molecular understanding, early detection, and targeted treatment of liver cancer DOI

Ji Shi,

Xu Zhu, Jun‐Bo Yang

et al.

World Journal of Hepatology, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 6, 2025

In this review, we explore the application of next-generation sequencing in liver cancer research, highlighting its potential modern oncology. Liver cancer, particularly hepatocellular carcinoma, is driven by a complex interplay genetic, epigenetic, and environmental factors. Key genetic alterations, such as mutations TERT, TP53, CTNNB1, alongside epigenetic modifications DNA methylation histone remodeling, disrupt regulatory pathways promote tumorigenesis. Environmental factors, including viral infections, alcohol consumption, metabolic disorders nonalcoholic fatty disease, enhance hepatocarcinogenesis. The tumor microenvironment plays pivotal role progression therapy resistance, with immune cell infiltration, fibrosis, angiogenesis supporting survival. Advances checkpoint inhibitors chimeric antigen receptor T-cell therapies have shown potential, but unique immunosuppressive milieu presents challenges. Dysregulation Wnt/β-catenin underscores need for targeted therapeutic strategies. Next-generation accelerating identification enabling more precise diagnosis personalized treatment plans. A deeper understanding these molecular mechanisms essential advancing early detection developing effective against cancer.

Language: Английский

Citations

1
UHRF1 inhibition epigenetically reprograms cancer stem cells to suppress the tumorigenic phenotype of hepatocellular carcinoma DOI Creative Commons
Yanchen Wang,

Pengchao Hu,

Fenfen Wang

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(6)

Published: June 28, 2023

Abstract Cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in many types of cancer, including hepatocellular carcinoma (HCC). Epigenetic reprogramming CSCs has emerged as a promising strategy for inducing the transition from malignancy benignity. Ubiquitin-like with PHD ring finger domains 1 (UHRF1) is required DNA methylation inheritance. Here, we investigated role mechanism UHRF1 regulating CSC properties evaluated impact targeting on HCC. Hepatocyte-specific Uhrf1 knockout (Uhrf1 HKO ) strongly suppressed initiation self-renewal both diethylnitrosamine (DEN)/CCl 4 -induced Myc -transgenic HCC mouse models. Ablation human cell lines yielded consistent phenotypes. Integrated RNA-seq whole genome bisulfite sequencing revealed widespread hypomethylation induced by silencing epigenetically reprogrammed cancer toward differentiation suppression. Mechanistically, deficiency upregulated CEBPA subsequently inhibited GLI1 Hedgehog signaling. Administration hinokitiol, potential inhibitor, significantly reduced growth phenotypes mice -driven Of pathophysiological significance, expression levels UHRF1, GLI1, key axis proteins consistently increased livers patients These findings highlight regulatory liver have important implications development therapeutic strategies

Language: Английский

Citations

16
Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma DOI Creative Commons
Eun-Jin Yun, Donghwi Kim, Sangwoo Kim

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 13, 2023

Abstract Glioblastoma (GBM) is the most malignant tumor in brain and highly resistant to therapy. Clinical evidence suggests increased number of cancer stem cells (CSCs) may contribute failure conventional therapies, but mechanisms associated with acquisition CSC properties GBM are not fully understood. We found that DAB2IP suppresses by targeting synaptic proteins neuroligin 3 (NLGN3) GBM. Furthermore, we showed GBM-derived NLGN3 has an oncogenic function inducing within Moreover, elevated transcription mediated Wnt/β-catenin signaling pathway resulted secretion into surrounding microenvironment. Both condition media containing recombinant transformed neighboring CSCs, suggesting as a critical component properties. NLGN3-bearing CSCs using upstream inhibitors synergistically enhances efficacy treatment. Hence, unveiled series regulatory for progression Wnt/β-catenin-mediated NLGN3. These results provide new strategy improve therapeutic treatments.

Language: Английский

Citations

14
LARP4B promotes hepatocellular carcinoma progression and impairs sorafenib efficacy by activating SPINK1-mediated EGFR pathway DOI Creative Commons
Chuanxu Wang, Rui Dong,

Feicheng Yang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 1, 2024

La-related proteins (LARPs) regulate gene expression by binding to RNAs and exhibit critical effects on disease progression, including tumors. However, the role of LARP4B its underlying mechanisms in progression hepatocellular carcinoma (HCC) remain largely unclear. In this study, we found that is upregulated correlates with poor prognosis patients HCC. Gain- loss-of-function assays showed promotes stemness, proliferation, metastasis, angiogenesis vitro vivo. Furthermore, inhibition enhances antitumor sorafenib blocks metastasis-enhancing low concentrations Mechanistically, METTL3-mediated N

Language: Английский

Citations

5
Post-translational modifications and immune responses in liver cancer DOI Creative Commons
Youwei Wang,

Jiachen Zuo,

Chong Chen

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 11, 2023

Post-translational modification (PTM) refers to the covalent attachment of functional groups protein substrates, resulting in structural and changes. PTMs not only regulate development progression liver cancer, but also play a crucial role immune response against cancer. Cancer immunity encompasses combined efforts innate adaptive surveillance tumor antigens, cells, tumorigenic microenvironments. Increasing evidence suggests that immunotherapies, which harness system’s potential combat can effectively improve cancer patient prognosis prolong survival. This review presents comprehensive summary current understanding key such as phosphorylation, ubiquitination, SUMOylation, glycosylation context Additionally, it highlights targets associated with these modifications enhance immunotherapies treatment

Language: Английский

Citations

12
Mitochondria’s Role in the Maintenance of Cancer Stem Cells in Hepatocellular Carcinoma DOI
Manar A. Elhinnawi,

Michael Ibrahim Boushra,

Donia Mohamed Hussien

et al.

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Language: Английский

Citations

3
Liver cancer stem cell dissemination and metastasis: uncovering the role of NRCAM in hepatocellular carcinoma DOI Creative Commons
Lingyun Zhou, Linye He, Changhai Liu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Nov. 22, 2023

Liver cancer stem cells (LCSCs) play an important role in hepatocellular carcinoma (HCC), but the mechanisms that link LCSCs to HCC metastasis remain largely unknown. This study aims reveal contributions of NRCAM LCSC function and metastasis, further explore its mechanism detail.117 29 non-HCC patients with focal liver lesions were collected analyzed assess association between metastasis. Single-cell RNA sequencing (scRNA-seq) was used biological characteristics high expression metastatic HCC. The dissemination explored vitro vivo using MYC-driven organoids from murine cells.Serum is associated poor prognosis. A scRNA-seq analysis identified highly expressed MYC activation Moreover, facilitated migration invasion, which confirmed organoids. tumor allografts demonstrated mediated intra-hepatic/lung by enhancing ability escape tumors into bloodstream. Nrcam inhibition blocked Mechanistically, activated epithelial-mesenchymal transition (EMT) metastasis-related matrix metalloproteinases (MMPs) through MACF1 β-catenin signaling pathway LCSCs.LCSCs typified have a strong invade migrate, factor leading

Language: Английский

Citations

8
Novel insights into the impact of liver inflammatory responses on primary liver cancer development DOI Creative Commons

Yeni Ait Ahmed,

Fouad Lafdil

Liver Research, Journal Year: 2023, Volume and Issue: 7(1), P. 26 - 34

Published: Feb. 3, 2023

Primary liver cancers rank among the deadliest worldwide and often develop in patients with chronic diseases an inflammatory context. This review highlights recent reports on mechanisms of inflammatory-mediated hepatic cell transformation that trigger tumorigenic process (initiation steps) impact immune response favoring tumor expansion (progression steps). Several cytokines, namely interleukin (IL)-6, IL-17, IL-1beta, necrosis factor-alpha, have been described to play a prominent role initiation cancers. Additionally, inflammation contributes cancer progression by escape from anti-tumor response, angiogenesis, metastasis through growth factor-beta matrix metalloprotease upregulation. These studies allowed development novel therapeutic strategies aiming at regulating inflammation. are based use anti-inflammatory agents, antibodies targeting checkpoint molecules such as programmed death ligand 1 angiogenic factors, key microRNAs involved development. aims summarizing reporting different which responses could contribute

Language: Английский

Citations

7
A Review of the Potential Role of CoQ10 in the Treatment of Hepatocellular Carcinoma DOI
Mahsa Liaghat, Mohammad Yaghoubzad-Maleki, Mohsen Nabi‐Afjadi

et al.

Biochemical Genetics, Journal Year: 2023, Volume and Issue: 62(2), P. 575 - 593

Published: Aug. 26, 2023

Language: Английский

Citations

7
Folate induces stemness and increases oxygen consumption under glucose deprivation by notch-1 pathway activation in colorectal cancer cell DOI

Juan Rodríguez Silva,

Matías Monsalves‐Álvarez, Carlos Sepúlveda

et al.

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

Language: Английский

Citations

2