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    GENE:

    WWTR1 (WW Domain Containing Transcription Regulator 1)

    i
    Other names: WWTR1, WW Domain Containing Transcription Regulator 1, TAZ, WW Domain-Containing Transcription Regulator Protein 1, Transcriptional Coactivator With PDZ-Binding Motif, DKFZp586I1419, Transcriptional Co-Activator With PDZ-Binding Motif
    11d
    Co-repression of Yap1 and Sox9 Abrogates Established Cholangiocarcinoma by Eliminating Transcriptional Compensation. (PubMed, bioRxiv)
    Co-targeting SOX9 and YAP1 offers a promising and safe broad-spectrum preventive/therapeutic approach for iCCA, potentially overcoming resistance to YAP1 inhibition. The adaptive resistance mechanism identified may extend to other malignancies, providing insights for addressing the advanced resistant to YAP1-TEAD-directed therapies.
    Journal
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    YAP1 (Yes associated protein 1) • SOX9 (SRY-Box Transcription Factor 9) • WWTR1 (WW Domain Containing Transcription Regulator 1) • MGAT5 (Alpha-1,6-Mannosylglycoprotein 6-Beta-N-Acetylglucosaminyltransferase) • TAFAZZIN (Tafazzin)
    21d
    One in one million - A case of pleural disease. (PubMed, Interdiscip Cardiovasc Thorac Surg)
    Treatment with the MEK inhibitor trametinib was initiated, but the patient died within three months. This case underscores the diagnostic challenges of EHE due to its rarity and variable clinical presentation, which often delays diagnosis until advanced stages. The report highlights the aggressive nature of pleural EHE and lack of standardised treatments, emphasising the need for early recognition.
    Journal
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    WWTR1 (WW Domain Containing Transcription Regulator 1) • CAMTA1 (Calmodulin Binding Transcription Activator 1)
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    Mekinist (trametinib)
    24d
    Targeting the USP7-PRMT6 epigenetic axis overcomes chemoresistance in breast cancer by coordinating H3R2me2a deposition and RNF168 methylation for DNA repair and ferroptosis blockade. (PubMed, Cell Death Differ)
    To translate this mechanism, we engineered an injectable hydrogel for the sequential co-delivery of cisplatin and PRMT6/USP7 inhibitors, demonstrating significantly enhanced therapeutic efficacy. Our study unveils a previously unrecognized bifunctional role for the PRMT6-USP7 axis in orchestrating epigenetic reprogramming and DNA repair to confer platinum resistance, providing profound mechanistic insights and a compelling co-targeting strategy for overcoming chemoresistance in breast cancer.
    Journal
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    WWTR1 (WW Domain Containing Transcription Regulator 1) • USP7 (Ubiquitin Specific Peptidase 7) • RNF168 (Ring Finger Protein 168)
    3ms
    Skin-analogue primary poroid neoplasms of the head and neck with YAP1/WWTR1::MAML2/NUTM1 fusions: clinicopathologic and genetic spectrum of a novel tumor family delineated in a series of 10 cases. (PubMed, Virchows Arch)
    Moreover, MAML2-fused cases might be confused with variant or high-grade mucoepidermoid carcinomas, as they share squamous phenotype and MAML2 rearrangements. The biology of bland cases and their nosology (benign vs low-grade malignant) remain to be further characterized.
    Journal
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    YAP1 (Yes associated protein 1) • WWTR1 (WW Domain Containing Transcription Regulator 1) • NUTM1 (NUT Midline Carcinoma Family Member 1) • MAML2 (Mastermind Like Transcriptional Coactivator 2)
    3ms
    A novel bispecific siRNA concept: Efficient dual knockdown of YAP1 and WWTR1 with a single guide strand. (PubMed, Mol Ther Nucleic Acids)
    Additionally, a chemically modified bispecific siRNA showed effective knockdown in vivo. Our data demonstrate the potential for using a bispecific siRNA targeting YAP1/WWTR1 as a therapeutic agent for liver diseases, presenting a novel approach for dual targeting with a simple conventional siRNA structure.
    Journal
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    YAP1 (Yes associated protein 1) • WWTR1 (WW Domain Containing Transcription Regulator 1)
    3ms
    Biomimetic core-shell breast cancer models using alginate, gelatin, and collagen I: simulating the tumor matrix for drug evaluation. (PubMed, Int J Biol Macromol)
    Breast cancer cells proliferated in the core of all prototypes designed, forming spheroids and cell aggregates with a high resistance to doxorubicin. The addition of Collagen I to the developed model enabled the upregulation of malignancy markers (Col1A1, Ki67, FOXC2, SNAI1, NFKB1, WWTR1), invasion markers (WASL, ACTA1, MYO1E, TPM4, PODXL, ITGA2, ITGA5, MENA, EGFR, CDC42), and drug resistance markers (ABCG2, CYP1A1, BAX, HSP90AA1) occurring in vivo. The developed 3D in vitro model can clarify the contribution of the extracellular matrix to the tumor outcome and drug efficacy by replicating some key characteristics of breast tumors, establishing a novel tool for chemotherapeutic agents and drug screening.
    Preclinical • Journal
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    EGFR (Epidermal growth factor receptor) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • BAX (BCL2-associated X protein) • COL1A1 (Collagen Type I Alpha 1 Chain) • WWTR1 (WW Domain Containing Transcription Regulator 1) • CDC42 (Cell Division Cycle 42) • PODXL (Podocalyxin) • SNAI1 (Snail Family Transcriptional Repressor 1) • TPM4 (Tropomyosin 4) • ACTA1 (Actin Alpha 1, Skeletal Muscle) • CYP1A1 (Cytochrome P450 Family 1 Subfamily A Member 1) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1) • ITGA2 (Integrin Subunit Alpha 2) • ITGA5 (Integrin Subunit Alpha 5) • FOXC2 (Forkhead Box C2)
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    doxorubicin hydrochloride
    3ms
    A cellular epithelioid hemangioma of the liver harboring a novel FOS::BCAR3 fusion gene. (PubMed, Virchows Arch)
    Furthermore, next-generation sequencing and Sanger sequencing demonstrated a FOS::BCAR3 fusion. To the best of our knowledge, this is the first reported case of cellular EH involving the liver and featuring a novel FOS::BCAR3 fusion, thereby broadening the spectrum of clinicopathological and genetic characteristics in this entity.
    Journal
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    CD34 (CD34 molecule) • CD31 (Platelet and endothelial cell adhesion molecule 1) • WWTR1 (WW Domain Containing Transcription Regulator 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1) • CAMTA1 (Calmodulin Binding Transcription Activator 1) • FOS (Fos Proto-Oncogene AP-1 Transcription Factor Subunit 2)
    3ms
    TRANSLATING MOLECULAR MECHANISMS OF EPITHELIOID HEMANGIOENDOTHELIOMA TO IMPROVE PATIENT OUTCOME. (PubMed, Crit Rev Oncol Hematol)
    These pathways also influence the tumor release of circulating cytokines, such as GDF-15 which is associated to patient outcomes. In this review we summarize advancements in the understanding of EHE biology that are closely associated with the EHE-specific translocations together with their implication for mechanisms that underpin EHE aggressiveness, with the final aim of highlighting EHE-related biomarkers and innovative therapeutic strategies.
    Review • Journal
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    YAP1 (Yes associated protein 1) • GDF15 (Growth differentiation factor 15) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • WWTR1 (WW Domain Containing Transcription Regulator 1) • CAMTA1 (Calmodulin Binding Transcription Activator 1) • TEAD1 (TEA Domain Transcription Factor 1)
    3ms
    Incidence, prevalence and treatment of patients with Epithelioid Haemangioendothelioma (EHE) in Canada: A Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) and Multi-pronged Canadian Research in Epithelioid Haemangioendothelioma (PRO_CARE EHE) study. (PubMed, Eur J Cancer)
    This is the largest series of EHE patients describing sequential systemic therapies. The role of systemic therapy in EHE in improving survival remains unclear and prospective studies with comparative arms are needed to add further insight into this chronic disease.
    Journal
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    YAP1 (Yes associated protein 1) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • WWTR1 (WW Domain Containing Transcription Regulator 1) • CAMTA1 (Calmodulin Binding Transcription Activator 1)
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    paclitaxel • pazopanib • sirolimus
    4ms
    The role of TEAD4 gene in the Hippo signaling pathway in triple-negative breast cancer and targeted therapy strategies. (PubMed, BMC Med Genomics)
    Through comprehensive analysis, we identified TEAD4 as a key gene in TNBC with high expression specificity. Irinotecan may be a potential targeted drug for TEAD4, offering a new therapeutic strategy for TNBC and potentially improving patient outcomes. Further experimental verification is required.
    Journal
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    WWTR1 (WW Domain Containing Transcription Regulator 1) • SOX11 (SRY-Box Transcription Factor 11) • TEAD4 (TEA Domain Transcription Factor 4)
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    irinotecan
    4ms
    C6orf223 promotes colorectal cancer growth and metastasis by facilitating PRMT5-MEP50 multiprotein complex assembling. (PubMed, J Clin Invest)
    Targeting C6orf223 using siRNAs encapsulated in ferritin protein shells effectively suppresses CRC tumor growth and metastasis. Collectively, our findings characterize the role of C6orf223 in facilitating PRMT5-MEP50 hetero-octameric complex assembling and suggest that C6orf223 could serve as a potential therapeutic target for CRC.
    Journal
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    FGFR1 (Fibroblast growth factor receptor 1) • WWTR1 (WW Domain Containing Transcription Regulator 1)