The developmental factor TBX3 engages with the Wnt/β-catenin transcriptional complex in colorectal cancer to regulate metastasis genes DOI Creative Commons
Amaia Jauregi‐Miguel, Simon Söderholm, Tamina Weiss

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(19)

Опубликована: Май 9, 2025

Wnt signaling orchestrates gene expression in a plethora of processes during development and adult cell homeostasis via the action nuclear β-catenin. Yet, little is known about how β-catenin generates context-specific transcriptional outcomes. Understanding this will reveal aberrant Wnt/β-catenin causes neoplasia specifically colorectal epithelium. We have previously identified transcription factor TBX3 as tissue-specific component complex mouse forelimb development. In study, we show that functionally active human cancer (CRC). Here, genome-wide binding transcriptomics analyses regulates metastasis genes cooperation with Wnt/β-catenin. Proteomics proximity labeling performed across pathway activation shows engages several factors chromatin remodeling complexes found at responsive elements (WRE). Protein sequence structure analysis revealed short motifs, including an exposed Asn-Pro-Phe (NPF), mediate these interactions. Deletion motifs abrogates TBX3’s to its protein partners ability enhance Wnt-dependent transcription. emerges key modulator oncogenic activity CRC, mechanism exposes protein-interaction surfaces putative druggable targets.

Язык: Английский

TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review) DOI Creative Commons
Zhimin Ye, Yongbin Hu

International Journal of Molecular Medicine, Год журнала: 2021, Номер 48(1)

Опубликована: Май 18, 2021

Idiopathic pulmonary fibrosis (IPF) is a worldwide disease characterized by the chronic and irreversible decline of lung function. Currently, there no drug to successfully treat except for transplantation. Numerous studies have been devoted study fibrotic process IPF findings showed that transforming growth factor‑β1 (TGF‑β1) plays central role in development IPF. TGF‑β1 promotes through various signaling pathways, including Smad, MAPK, ERK pathways. There are intersections between these which provide new targets researchers drugs. In addition, can affect affecting oxidative stress, epigenetics other aspects. Most processes involved promote IPF, but also inhibit it. This review discusses

Язык: Английский

Процитировано

137
Mechanistic insights into Wnt–β-catenin pathway activation and signal transduction DOI
Madelon M. Maurice, Stéphane Angers

Nature Reviews Molecular Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Язык: Английский

Процитировано

6
Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways DOI Creative Commons
Mahshid Deldar Abad Paskeh,

Sepideh Mirzaei,

Milad Ashrafizadeh

и другие.

Journal of Hepatocellular Carcinoma, Год журнала: 2021, Номер Volume 8, С. 1415 - 1444

Опубликована: Ноя. 1, 2021

Abstract: Liver cancers cause a high rate of death worldwide and hepatocellular carcinoma (HCC) is considered as the most common primary liver cancer. HCC remains challenging disease to treat. Wnt/β-catenin signaling pathway tumor-promoting factor in various cancers; hence, present review focused on role Wnt HCC, its association with progression therapy response based pre-clinical clinical evidence. The nuclear translocation β-catenin enhances expression level genes such c-Myc MMPs increasing cancer progression. mutation CTNNB1 gene encoding overexpression can lead stem cell features promotes their growth rate. Furthermore, prevents apoptosis cells increases migration via triggering EMT upregulating MMP levels. It suggested that participates mediating drug resistance immuno-resistance HCC. Upstream mediators including ncRNAs regulate Anti-cancer agents inhibit mediate proteasomal degradation therapy. studies have revealed ( CTNBB1 ) Based these subjects, future experiments focus developing novel therapeutics targeting Keywords: cancer, resistance, immunotherapy, signaling, non-coding RNAs

Язык: Английский

Процитировано

104
Walking the tight wire between cell adhesion and WNT signalling: a balancing act for β-catenin DOI Creative Commons
Tanne van der Wal, Renée van Amerongen

Open Biology, Год журнала: 2020, Номер 10(12)

Опубликована: Дек. 1, 2020

CTNNB1 (catenin β-1, also known as β-catenin) plays a dual role in the cell. It is key effector of WNT/CTNNB1 signalling, acting transcriptional co-activator TCF/LEF target genes. crucial for cell adhesion and critical component cadherin-based adherens junctions. Two functional pools CTNNB1, transcriptionally active an adhesive pool, can therefore be distinguished. Whether cells merely balance distribution available between these or whether interplay occurs them has long been studied debated. While indicated upon artificial modulation cadherin expression levels during epithelial–mesenchymal transition, it unclear to what extent exchange under physiological conditions response WNT stimulation. Here, we review evidence both models, discuss how binding its many interaction partners controlled propose avenues future studies.

Язык: Английский

Процитировано

75
Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling DOI Creative Commons
Kinjal Shah, Julhash U. Kazi

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Март 14, 2022

WNT/β-catenin signaling is a highly complex pathway that plays diverse roles in various cellular processes. While WNT ligands usually signal through their dedicated Frizzled receptors, the decision to β-catenin-dependent or -independent manner rests upon type of co-receptors used. Canonical β-catenin-dependent, whereas non-canonical β-catenin-independent according classical definition. This still holds true, albeit with some added complexity, as both pathways seem cross-talk intertwined networks involve use different ligands, and co-receptors. β-catenin can be directly phosphorylated by kinases governing its participation either canonical pathways. Moreover, co-activators associate determine output terms induction genes promoting proliferation differentiation. In this review, we provide an overview how protein phosphorylation controls signaling, particularly human cancer.

Язык: Английский

Процитировано

57
hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells DOI Creative Commons
Shenglei Feng, Jinmei Li, Hui Wen

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 23, 2022

Coordinated regulation of alternative pre-mRNA splicing is essential for germ cell development. However, the underlying molecular mechanism that controls mRNA expression during development remains elusive. Herein, we show hnRNPH1 highly expressed in reproductive system and recruits PTBP2 SRSF3 to modulate cells. Conditional knockout Hnrnph1 spermatogenic cells causes many abnormal events, thus affecting genes related meiosis communication between Sertoli This characterized by asynapsis chromosomes impairment germ-Sertoli communications, which ultimately leads male sterility. Markedly, germline-specific mutant female mice are also infertile, Hnrnph1-deficient oocytes exhibit a similar defective synapsis cell-cell junction as seen Collectively, our data support model wherein governs network events via recruitment SRSF3.

Язык: Английский

Процитировано

43
β-catenin inhibitors in cancer therapeutics: intricacies and way forward DOI Open Access

Arundhathi Dev,

Meenakshi Vachher, Chandra Prakash Prasad

и другие.

Bioengineered, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 1, 2023

β-catenin is an evolutionary conserved, quintessential, multifaceted protein that plays vital roles in cellular homeostasis, embryonic development, organogenesis, stem cell maintenance, proliferation, migration, differentiation, apoptosis, and pathogenesis of various human diseases including cancer. manifests both signaling adhesive features. It acts as a pivotal player intracellular component versatile WNT cascade involved homeostasis well carcinogenesis. also Ca2+ dependent adhesion via interaction with E-cadherin at the adherens junctions. Aberrant expression its nuclear accumulation promote transcription oncogenes c-Myc cyclinD1, thereby contributing to tumor initiation, progression. β-catenin's closely regulated levels stability, sub-cellular localization, transcriptional activity. Understanding molecular mechanisms regulation atypical will provide researchers not only novel insights into progression cancer but help deciphering new therapeutic avenues. In present review, we have summarized dual functions β-catenin, role signaling, associated mutations carcinogenesis cancers. Additionally, discussed challenges targeting molecule presently available drugs suggested possible way forward designing alternatives against this oncogene.

Язык: Английский

Процитировано

26
The role of MicroRNAs in mesenchymal stem cell differentiation into vascular smooth muscle cells DOI Creative Commons
Yasin Ahmadi, Sakhavat Abolhasani,

Yavar Rostami

и другие.

Cell Division, Год журнала: 2025, Номер 20(1)

Опубликована: Март 7, 2025

Язык: Английский

Процитировано

2
The WNT/β‐catenin dependent transcription: A tissue‐specific business DOI Creative Commons
Simon Söderholm, Claudio Cantù

WIREs Mechanisms of Disease, Год журнала: 2020, Номер 13(3)

Опубликована: Окт. 21, 2020

Abstract β‐catenin‐mediated Wnt signaling is an ancient cell‐communication pathway in which β‐catenin drives the expression of certain genes as a consequence trigger given by extracellular WNT molecules. The events occurring from signal to transcription are evolutionarily conserved, and their final output orchestrates countless processes during embryonic development tissue homeostasis. Importantly, dysfunctional Wnt/β‐catenin causes developmental malformations, its aberrant activation root several types cancer. A rich literature describes multitude nuclear players that cooperate with generate transcriptional program. However, unified theory how target gene still missing. We will discuss two interactors: factors allow localize at regions on DNA, co‐factors ultimately activate expression. In contrast presumed universality β‐catenin's action, ensemble available evidence suggests view complex system responses different cells tissues. malleable armamentarium might interact order right “canonical” targets each tissue, stage, or disease context. Discovering mechanism tissue‐specific response executed be crucial comprehend seemingly universal fosters wide spectrum Perhaps more importantly, this could inform us about tumor‐specific components need targeted dampen activity oncogenic β‐catenin. This article categorized under: Cancer > Molecular Cellular Physiology Genetics/Genomics/Epigenetics Stem Cells Development

Язык: Английский

Процитировано

67
Epigenetic Regulation of the Wnt/β-Catenin Signaling Pathway in Cancer DOI Creative Commons
Ankita Sharma,

Rafeeq Mir,

Sanjeev Galande

и другие.

Frontiers in Genetics, Год журнала: 2021, Номер 12

Опубликована: Сен. 6, 2021

Studies over the past four decades have elucidated role of Wnt/β-catenin mediated regulation in cell proliferation, differentiation and migration. These processes are fundamental to embryonic development, regeneration potential tissues, as well cancer initiation progression. In this review, we focus on epigenetic players which influence pathway via modulation its components coordinated Wnt target genes. The played by crosstalk with other signaling pathways mediating tumorigenesis is also elaborated. Hippo/YAP particularly emphasized due extensive destruction complex. Further, highlight recent advances developing therapeutic interventions targeting machinery based characterization these regulatory networks for effective treatment various cancers regenerative therapies.

Язык: Английский

Процитировано

52