ArticleSignal transduction and targeted therapy2023
B-lymphoid tyrosine kinase-mediated FAM83A phosphorylation elevates pancreatic tumorigenesis through interacting with β-catenin.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 46 citations in OpenAlex.
- Glutathione metabolism-linked ferroptosis in human seminoma: a spatial multi-omics mapping study.Redox biology · 2026Article
- Post-Translational Modifications in Pancreatic Cancer: Mechanisms to Clinical Applications.Journal of gastroenterology and hepatology · 2026Review
- Metastasis-SpecificJournal of clinical medicine · 2026Article
- LLPS-based classification and a novel prognostic signature reveal NRF1 as a therapeutic target in pancreatic cancer.Cancer cell international · 2026Article
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Pancreatic cancer EMT‑targeted therapy: Molecular mechanisms and clinical translation (Review).International journal of oncology · 2026Review
- Peptide Drugs in Gastrointestinal Tumors: Integrating Targeting, Delivery, and Therapeutic Actions for Synergistic Strategies.Biomolecules · 2026Review
- Targeting FAM83D triggers tumor cell senescence via cGAS-STING signaling activation and reprograms TAMs to combat glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- A Small-Molecule SLD1121 Activates Wnt/β-Catenin Signaling and Promotes Hair Growth via Targeting the Wnt Coreceptor LRP6.JACS Au · 2026Article
- M2 macrophage-derived extracellular vesicles induce EMT-like transcriptional reprogramming in colorectal cancer cells via upregulation of FAM83A.Scientific reports · 2026Article
- CKAAKN peptide-conjugated long-circulating nanoliposomes for the targeted delivery of oridonin to pancreatic cancers.Scientific reports · 2026Article
- tRNA mMolecular cancer · 2026Article
- Development and validation of a nomogram for predicting distant metastasis and prognosis in elderly T1-T2 pancreatic ductal adenocarcinoma patients.Discover oncology · 2026Article
- Article
- Secreted frizzled-related proteins in angiogenesis: molecular mechanisms and clinical implications.Angiogenesis · 2025Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- FAM83A is a prognostic biomarker for lung squamous cell carcinoma and correlated with immunoregulation.Scientific reports · 2025Article
- Deciphering the prognostic signature of nonsmall cell lung cancer using cisplatin resistance and circulating tumor cell-related gene analysis.3 Biotech · 2025Article
- The complex role and molecular mechanism of family with sequence similarity genes in cancer: a comprehensive review.Discover oncology · 2025Review
- TFAP2A upregulates FAM83A to suppress ferroptosis and diminish cisplatin sensitivity in non-small cell lung cancer.Cell division · 2025Article
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal activation of Wnt/β-catenin-mediated transcription is closely associated with the malignancy of pancreatic cancer. Family with sequence similarity 83 member A (FAM83A) was shown recently to have oncogenic effects in a variety of cancer types, but the biological roles and molecular mechanisms of FAM83A in pancreatic cancer need further investigation. Here, we newly discovered that FAM83A binds directly to β-catenin and inhibits the assembly of the cytoplasmic destruction complex thus inhibiting the subsequent phosphorylation and degradation. FAM83A is mainly phosphorylated by the SRC non-receptor kinase family member BLK (B-lymphoid tyrosine kinase) at tyrosine 138 residue within the DUF1669 domain that mediates the FAM83A-β-catenin interaction. Moreover, FAM83A tyrosine 138 phosphorylation enhances oncogenic Wnt/β-catenin-mediated transcription through promoting β-catenin-TCF4 interaction and showed an elevated nucleus translocation, which inhibits the recruitment of histone deacetylases by TCF4. We also showed that FAM83A is a direct downstream target of Wnt/β-catenin signaling and correlates with the levels of Wnt target genes in human clinical pancreatic cancer tissues. Notably, the inhibitory peptides that target the FAM83A-β-catenin interaction significantly suppressed pancreatic cancer growth and metastasis in vitro and in vivo. Our results revealed that blocking the FAM83A cascade signaling defines a therapeutic target in human pancreatic cancer.
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