ArticleCancer research2017
SPINK6 Promotes Metastasis of Nasopharyngeal Carcinoma via Binding and Activation of Epithelial Growth Factor Receptor.
Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- SPINK2 in hematopoiesis and cancer: Biology and clinical implications.Cell death discovery · 2026Review
- An exploratory study on the potential of angiogenic genes in early HNSCC detection.Discover oncology · 2025Article
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- BAP31-ELAVL1-SPINK6 axis induces loss of cell polarity and promotes metastasis in hepatocellular carcinoma.International journal of biological sciences · 2025Article
- Integration RNA bulk and single cell RNA sequencing to explore the change of glycolysis-related immune microenvironment and construct prognostic signature in head and neck squamous cell carcinoma.Translational oncology · 2024Article
- Therapeutic potential of the secreted Kazal-type serine protease inhibitor SPINK4 in colitis.Nature communications · 2024Article
- ECRG2/SPINK7 Tumor Suppressor as Modulator of DNA Damage Response.International journal of molecular sciences · 2024Review
- TSPAN1 inhibits metastasis of nasopharyngeal carcinoma via suppressing NF-kB signaling.Cancer gene therapy · 2024Article
- Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics.Translational cancer research · 2024Article
- IL-13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation.JCI insight · 2023Article
- Extensive set of African ancestry-informative markers (AIMs) to study ancestry and population health.Frontiers in genetics · 2023Article
- LHX2 facilitates the progression of nasopharyngeal carcinoma via activation of the FGF1/FGFR axis.British journal of cancer · 2022Article
- Bioinformatics analysis identifies potential biomarkers involved in the metastasis of locoregionally advanced nasopharyngeal carcinoma.Medicine · 2022Article
- Aberrant miR-874-3p/leptin/EGFR/c-Myc signaling contributes to nasopharyngeal carcinoma pathogenesis.Journal of experimental & clinical cancer research : CR · 2022Article
- SPINK6 inhibits human airway serine proteases and restricts influenza virus activation.EMBO molecular medicine · 2022Article
- Shrew's venom quickly causes circulation disorder, analgesia and hypokinesia.Cellular and molecular life sciences : CMLS · 2022Article
- SPINKs in Tumors: Potential Therapeutic Targets.Frontiers in oncology · 2022Review
- Rare case of metachronous tumor: Nasopharyngeal and colorectal carcinoma.Experimental and therapeutic medicine · 2021Article
- Article
- Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment.Cancers · 2021Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Nasopharyngeal carcinoma has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. The underlying molecular mechanisms of nasopharyngeal carcinoma metastasis are not fully understood. Here, we report the identification of serine protease inhibitor Kazal-type 6 (SPINK6) as a functional regulator of nasopharyngeal carcinoma metastasis via EGFR signaling. SPINK6 mRNA was upregulated in tumor and highly metastatic nasopharyngeal carcinoma cells. Immunohistochemical staining of 534 nasopharyngeal carcinomas revealed elevated SPINK6 expression as an independent unfavorable prognostic factor for overall, disease-free, and distant metastasis-free survival. Ectopic SPINK6 expression promoted in vitro migration and invasion as well as in vivo lymph node metastasis and liver metastasis of nasopharyngeal carcinoma cells, whereas silencing SPINK6 exhibited opposing effects. SPINK6 enhanced epithelial-mesenchymal transition by activating EGFR and the downstream AKT pathway. Inhibition of EGFR with a neutralizing antibody or erlotinib reversed SPINK6-induced nasopharyngeal carcinoma cell migration and invasion. Erlotinib also inhibited SPINK6-induced metastasis in vivo Notably, SPINK6 bound to the EGFR extracellular domain independent of serine protease-inhibitory activity. Overall, our results identified a novel EGFR-activating mechanism in which SPINK6 has a critical role in promoting nasopharyngeal carcinoma metastasis, with possible implications as a prognostic indicator in nasopharyngeal carcinoma patients. Cancer Res; 77(2); 579-89. ©2016 AACR.
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