WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(2), P. 727 - 746

Published: April 8, 2023

Hepatocellular carcinoma (HCC) is a liver cancer, highly heterogeneous both at the histopathological and molecular levels. It arises from hepatocytes as result of accumulation numerous genomic alterations in various signaling pathways, including canonical WNT/β-catenin, AKT/mTOR, MAPK pathways well associated with telomere maintenance, p53/cell cycle regulation, epigenetic modifiers, oxidative stress. The role WNT/β-catenin homeostasis regeneration established, whereas development progression HCC extensively studied. Herein, we review recent advances our understanding how facilitates development, acquisition stemness features, metastasis, resistance to treatment. We outline genetic that lead activated HCC. discuss pivotal roles CTNNB1 mutations, aberrantly expressed non-coding RNAs complexity crosstalk between other challenging or advantageous aspects therapy stratification patients for

Language: Английский

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Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 25, 2025

The hepatocyte growth factor (HGF) along with its receptor (c-MET) are crucial in preserving standard cellular physiological activities, and imbalances the c-MET signaling pathway can lead to development advancement of tumors. It has been extensively demonstrated that immune checkpoint inhibitors (ICIs) result prolonged remission certain patients. Nevertheless, numerous preclinical studies have shown MET imbalance hinders effectiveness anti-PD-1/PD-L1 treatments through various mechanisms. Consequently, clarifying link between tumor microenvironment (TME), as well uncovering effects anti-MET treatment on ICI therapy, is for enhancing outlook In this review, we examine impact abnormal activation HGF/c-MET control TME processes governing PD-L1 expression cancer cells. review thoroughly examines both clinical practical evidence regarding use alongside PD-1/PD-L1 inhibitors, emphasizing focusing immunotherapy enhances treating tumors exhibiting elevated expression.

Language: Английский

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Hepatic Iron Overload and Hepatocellular Carcinoma: New Insights into Pathophysiological Mechanisms and Therapeutic Approaches

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 392 - 392

Published: Jan. 24, 2025

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is rising in global incidence and mortality. Metabolic dysfunction-associated steatotic disease (MASLD), one leading causes chronic disease, strongly linked to metabolic conditions that can progress cirrhosis HCC. Iron overload (IO), whether inherited or acquired, results abnormal iron hepatic deposition, significantly impacting MASLD development progression While pathophysiological connections between IO, MASLD, HCC are not fully understood, dysregulation glucose lipid metabolism IO-induced oxidative stress being investigated as drivers. Genomic analyses IO reveal inconsistencies association certain mutations with malignancies. Moreover, also associated hepcidin activation ferroptosis, representing promising targets for risk assessment therapeutic intervention. Understanding relationship essential advancing clinical strategies against progression, particularly recent IO-targeted therapies showing potential at improving biochemistry insulin sensitivity. In this review, we summarize current evidence on HCC, underscoring importance early diagnosis, stratification, targeted treatment these interconnected conditions.

Language: Английский

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The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: Jan. 15, 2022

Abstract Canonical Wnt/β-catenin signaling is a complex cell-communication mechanism that has central role in the progression of various cancers. The cellular factors participate regulation this are still not fully elucidated. Lysine acetylation significant protein modification which facilitates reversible target function dependent on activity lysine acetyltransferases (KATs) and catalytic deacetylases (KDACs). Protein been classified into histone non-histone acetylation. Histone kind epigenetic modification, it can modulate transcription important biological molecules signaling. Additionally, as type post-translational directly alters core Conversely, regulate expression based or To date, inhibitors targeting KATs KDACs have discovered, some these exert their anti-tumor via blocking Here, we discuss available evidence understanding complicated interaction with signaling, new for cancer therapy controlling

Language: Английский

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Role of β-Catenin Activation in the Tumor Immune Microenvironment and Immunotherapy of Hepatocellular Carcinoma

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2311 - 2311

Published: April 15, 2023

Recently, the therapeutic combination of atezolizumab and bevacizumab was widely used to treat advanced hepatocellular carcinoma (HCC). According recent clinical trials, immune checkpoint inhibitors (ICIs) molecular target agents are expected be key strategies in future. Nonetheless, mechanisms underlying responses evasion remain unclear. The tumor microenvironment plays a vital role HCC progression. infiltration CD8-positive cells into tumors expression molecules factors this microenvironment. Specifically, Wnt/β catenin pathway activation causes “immune exclusion”, associated with poor cells. Some studies suggested an association between ICI resistance β-catenin HCC. Additionally, several subclassifications were proposed. can broadly divided inflamed class non-inflamed class, subclasses. mutations important subclasses; may useful when considering as serve biomarker for ICI. Various types modulators developed. Several kinases also involved pathway. Therefore, combinations modulators, kinase inhibitors, ICIs exert synergistic effects.

Language: Английский

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Functional Roles of Bromodomain Proteins in Cancer

Cancers, Journal Year: 2021, Volume and Issue: 13(14), P. 3606 - 3606

Published: July 19, 2021

Histone acetylation is generally associated with an open chromatin configuration that facilitates many cellular processes including gene transcription, DNA repair, and replication. Aberrant levels of histone lysine are the development cancer. Bromodomains represent a family structurally well-characterized effector domains recognize acetylated lysines in chromatin. As part their fundamental reader activity, bromodomain-containing proteins play versatile roles epigenetic regulation, additional functional modules often present same protein, or through assembly larger enzymatic complexes. Dysregulated expression, chromosomal translocations, and/or mutations have been correlated poor patient outcomes Thus, bromodomains emerged as highly tractable class targets due to well-defined structural domains, increasing ease designing screening for molecules modulate reading process. Recent developments pharmacological agents target specific has helped understand diverse mechanisms interaction partners variety processes, provide promise applying bromodomain inhibitors into clinical field cancer treatment. In this review, we explore expression protein interactome profiles discuss them terms groups. Furthermore, highlight our current understanding cancer, well emerging strategies specifically bromodomains, combination therapies using alongside traditional therapeutic approaches designed re-program tumorigenesis metastasis.

Language: Английский

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WNT5A: a double-edged sword in colorectal cancer progression

Mutation Research/Reviews in Mutation Research, Journal Year: 2023, Volume and Issue: 792, P. 108465 - 108465

Published: July 1, 2023

Language: Английский

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CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(5)

Published: May 17, 2022

Circular RNAs have been reported to play essential roles in the tumorigenesis and progression of various cancers. However, biological processes mechanisms involved hepatocellular carcinoma (HCC) remain unclear. Initial RNA-sequencing data qRT-PCR results our cohort showed that hsa_circ_0072309 (also called circLIFR) was markedly downregulated HCC tissues. Kaplan-Meier analysis indicated higher levels circLIFR patients correlated with favorable overall survival recurrence-free rates. Both vitro vivo experiments inhibited proliferation invasion abilities cells. We therefore conducted related explore mechanism HCC. Fluorescence situ hybridization revealed mainly located cytoplasm, RNA immunoprecipitation assays significantly enriched by Ago2 protein. These suggested may function as a sponge miRNAs regulate progression. further bioinformatics prediction well dual-luciferase reporter assays, which could miR-624-5p stabilize glycogen synthase kinase 3β (GSK-3β) expression. Loss gain demonstrated regulation expression or GSK-3β affected induced circLIFR. Importantly, we also proved facilitate degradation β-catenin prevent its translocation nucleus Overall, study acts tumor suppressor regulating inactivating GSK-3β/β-catenin signaling pathway.

Language: Английский

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Long Non-Coding RNA RFPL3S Functions as a Biomarker of Prognostic and Immunotherapeutic Prediction in Testicular Germ Cell Tumor

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 20, 2022

The incidence of testicular germ cell tumor (TGCT) is currently on the rise worldwide, which 15%-30% patients have occur recurrence and metastasis. However, clinical methods for diagnosing TGCT judging its prognosis remained inadequate. In this study, we aimed to explore possibility testis-specific long-chain non-coding RNA (lncRNA) Ret finger protein-like 3S (RFPL3S) as a biomarker diagnosis, prognosis, treatment response by reviewing gene expression data in Gene Expression Omnibus (GEO) Cancer Genome Atlas (TCGA) databases. cohort DNA methylation TCGA were downloaded from TGCA, UCSC XENA, GEO. bioinformatic tools used, including GEPIA2, Kaplan-Meier Plotter, LinkedOmics, Sangerbox Tools, GSCA, Tumor Immune Dysfunction Exclusion. Compared with normal tissues, RFPL3S was significantly reduced TGCT, negatively correlated patient’s Tumor, Node, Metastasis stage. Hypermethylation low copy number present associated short disease-free progression-free intervals. Silencing enhanced invasion ability proliferation cells evaluated Transwell CCK-8 experiments. Additionally, positively infiltration immune-activating such B cells, CD8+ T cytotoxic natural killer immunosuppressive Th17 Th2. Higher immunotherapy benefits. conclusion, determined that lncRNA functioned suppressor could be used prognostic predictor well marker predict effect immunotherapy.

Language: Английский

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Research on the signaling pathways related to the intervention of traditional Chinese medicine in Parkinson's disease:A literature review

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 326, P. 117850 - 117850

Published: Feb. 6, 2024

Language: Английский

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