The Hippo signaling pathway in gastric cancer DOI Creative Commons
Zhifa Cao, Liwei An, Yi Han

et al.

Acta Biochimica et Biophysica Sinica, Journal Year: 2023, Volume and Issue: unknown

Published: March 1, 2023

Gastric cancer (GC) is an aggressive malignant disease which still lacks effective early diagnosis markers and targeted therapies, representing the fourth-leading cause of cancer-associated death worldwide. The Hippo signaling pathway plays crucial roles in organ size control tissue homeostasis under physiological conditions, yet its aberrations have been closely associated with several hallmarks cancer. last decade witnessed a burst investigations dissecting how dysregulation contributes to tumorigenesis, highlighting therapeutic potential targeting this for tumor intervention. In review, we systemically document studies on contexts gastric initiation, progression, metastasis, acquired drug resistance, emerging development Hippo-targeting strategies. By summarizing major open questions field, aim inspire further in-depth understanding GC development, as well translational implications treatment.

Language: Английский

Therapeutic targeting of TEAD transcription factors in cancer DOI
Ajaybabu V. Pobbati, Ramesh Kumar, Brian P. Rubin

et al.

Trends in Biochemical Sciences, Journal Year: 2023, Volume and Issue: 48(5), P. 450 - 462

Published: Jan. 26, 2023

Language: Английский

Citations

83
Control of stem cell renewal and fate by YAP and TAZ DOI
Jordan H. Driskill, Duojia Pan

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(12), P. 895 - 911

Published: Aug. 25, 2023

Language: Английский

Citations

72
Direct and selective pharmacological disruption of the YAP–TEAD interface by IAG933 inhibits Hippo-dependent and RAS–MAPK-altered cancers DOI Creative Commons
Emilie A. Chapeau, Laurent Sansregret, Giorgio Giacomo Galli

et al.

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(7), P. 1102 - 1120

Published: April 2, 2024

The YAP-TEAD protein-protein interaction mediates YAP oncogenic functions downstream of the Hippo pathway. To date, available pharmacologic agents bind into lipid pocket TEAD, targeting indirectly via allosteric changes. However, consequences a direct pharmacological disruption interface between and TEADs remain largely unexplored. Here, we present IAG933 its analogs as potent first-in-class selective disruptors with suitable properties to enter clinical trials. Pharmacologic abrogation all four TEAD paralogs resulted in eviction from chromatin reduced Hippo-mediated transcription induction cell death. In vivo, deep tumor regression was observed Hippo-driven mesothelioma xenografts at tolerated doses animal models well Hippo-altered cancer outside mesothelioma. Importantly this also extended larger indications, such lung, pancreatic colorectal cancer, combination RTK, KRAS-mutant MAPK inhibitors, leading more efficacious durable responses. Clinical evaluation is underway.

Language: Английский

Citations

37
Pioneer factor GATA6 promotes colorectal cancer through 3D genome regulation DOI Creative Commons
Huijue Lyu, X.-X. Chen,

Yang Cheng

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(6)

Published: Feb. 7, 2025

Colorectal cancer (CRC) is one of the most lethal and prevalent malignancies. While overexpression pioneer factor GATA6 in CRC has been linked with metastasis, its role genome-wide gene expression dysregulation remains unclear. Through studies primary human tissues analysis TCGA data, we found that preferentially binds at CRC-specific active enhancers, enrichment enhancer-promoter loop anchors. protein also physically interacts CTCF, suggesting critical 3D genome organization. The ablation through AID CRISPR systems severely impaired cell clonogenicity proliferation. Mechanistically, knockout induced global loss open chromatins extensive alterations interactions for oncogenes. Last, showed greatly reduced tumor growth improved survival mice. Together, revealed a previously unidentified mechanism by which contributes to pathogenesis colorectal cancer.

Language: Английский

Citations

3
The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance DOI Creative Commons
Serena Diazzi, Sophie Tartare‐Deckert, Marcel Deckert

et al.

Oncogenesis, Journal Year: 2023, Volume and Issue: 12(1)

Published: Feb. 11, 2023

Abstract Advanced cutaneous melanoma is the deadliest form of skin cancer and one most aggressive human cancers. Targeted therapies (TT) against BRAF mutated immune checkpoints blockade (ICB) have been a breakthrough in treatment metastatic melanoma. However, therapy-driven resistance remains major hurdle clinical management disease. Besides shaping tumor microenvironment, current treatments impact transition states to promote cell phenotypic plasticity intratumor heterogeneity, which compromise efficacy outcomes. In this context, mesenchymal-like dedifferentiated cells exhibit remarkable ability autonomously assemble their own extracellular matrix (ECM) biomechanically adapt response therapeutic insults, thereby fueling relapse. Here, we review recent studies that highlight mechanical as hallmark adaptive non-genetic emerging driver cross-resistance TT ICB. We also discuss how targeting BRAF-mutant ECM-based mechanotransduction pathways may overcome cross-resistance.

Language: Английский

Citations

30
Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases DOI Creative Commons
Priyanka Dey Talukdar, Urmi Chatterji

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 13, 2023

Abstract Specific cell states in metazoans are established by the symphony of gene expression programs that necessitate intricate synergic interactions between transcription factors and co-activators. Deregulation these regulatory molecules is associated with state transitions, which turn accountable for diverse maladies, including developmental disorders, metabolic most significantly, cancer. A decade back factors, key enablers disease development, were historically viewed as ‘undruggable’; however, intervening years, a wealth literature validated they can be targeted indirectly through transcriptional co-activators, their confederates various physiological molecular processes. These along have ability to initiate modulate genes necessary normal functions, whereby, deregulation such may foster tissue-specific phenotype. Hence, it essential analyze how co-activators specific multilateral processes coordination other factors. The proposed review attempts elaborate an in-depth account involvement regulation, context-specific contributions pathophysiological conditions. This also addresses issue has not been dealt comprehensive manner hopes direct attention towards future research will encompass patient-friendly therapeutic strategies, where drugs targeting enhanced benefits reduced side effects. Additional insights into currently available interventions constraints eventually reveal multitudes advanced targets aiming amelioration good patient prognosis.

Language: Английский

Citations

26
YAP/TAZ: Molecular pathway and disease therapy DOI Creative Commons

Yuzi Wei,

Victoria Lee Zhi Hui,

Yilin Chen

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: Aug. 1, 2023

The Yes-associated protein and its transcriptional coactivator with PDZ-binding motif (YAP/TAZ) are two homologous coactivators that lie at the center of a key regulatory network Hippo, Wnt, GPCR, estrogen, mechanical, metabolism signaling. YAP/TAZ influences expressions downstream genes proteins as well enzyme activity in metabolic cycles, cell proliferation, inflammatory factor expression, transdifferentiation fibroblasts into myofibroblasts. can also be regulated through epigenetic regulation posttranslational modifications. Consequently, function these mechanisms implicates pathogenesis metabolism-related diseases, atherosclerosis, fibrosis, delicate equilibrium between cancer progression organ regeneration. As such, there arises pressing need for thorough investigation clinical settings. In this paper, we aim to elucidate signaling pathways regulate explore YAP/TAZ-induce diseases their potential therapeutic interventions. Furthermore, summarize current studies investigating treatments targeting YAP/TAZ. We address limitations existing research on propose future directions research. conclusion, review aims provide fresh insights mediated by identify targets present innovative solutions overcome challenges associated

Language: Английский

Citations

24
Hippo pathway in non-small cell lung cancer: mechanisms, potential targets, and biomarkers DOI Creative Commons
Hongge Liang, Yan Xu, Jing Zhao

et al.

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(5), P. 652 - 666

Published: March 18, 2024

Abstract Lung cancer is the primary contributor to cancer-related deaths globally, and non-small cell lung (NSCLC) constitutes around 85% of all cases. Recently, emergence targeted therapy immunotherapy revolutionized treatment NSCLC greatly improved patients’ survival. However, drug resistance inevitable, extensive research has demonstrated that Hippo pathway plays a crucial role in development NSCLC. The highly conserved signaling essential for various biological processes, including organ development, maintenance epithelial balance, tissue regeneration, wound healing, immune regulation. This exerts its effects through two key transcription factors, namely Yes-associated protein (YAP) transcriptional co-activator PDZ-binding motif (TAZ). They regulate gene expression by interacting with transcriptional-enhanced associate domain (TEAD) family. In recent years, this been extensively studied review summarizes comprehensive overview involvement NSCLC, discusses mechanisms resistance, potential targets, biomarkers associated

Language: Английский

Citations

15
Single-cell analyses reveal transient retinal progenitor cells in the ciliary margin of developing human retina DOI Creative Commons
Birthe Dorgau,

Joseph Collin,

Agata Rozanska

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 26, 2024

The emergence of retinal progenitor cells and differentiation to various cell types represent fundamental processes during development. Herein, we provide a comprehensive single characterisation transcriptional chromatin accessibility changes that underline specification over the course human development up midgestation. Our lineage trajectory data demonstrate presence early progenitors, which transit late, further transient neurogenic give rise all neurons. Combining RNA-Seq with spatial transcriptomics eye samples, progenitors in ciliary margin zone decreasing occurrence from 8 post-conception week In cells, identified significant enrichment for enhanced associate domain transcription factor binding motifs, when inhibited led loss cycling identity pluripotent stem derived organoids.

Language: Английский

Citations

15
Compressive stresses in cancer: characterization and implications for tumour progression and treatment DOI

Julia A Linke,

Lance L. Munn, Rakesh K. Jain

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(11), P. 768 - 791

Published: Oct. 10, 2024

Language: Английский

Citations

11