AHNAK is downregulated in melanoma, predicts poor outcome, and may be required for the expression of functional cadherin-1
| العنوان: | AHNAK is downregulated in melanoma, predicts poor outcome, and may be required for the expression of functional cadherin-1 |
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| المؤلفون: | Jennifer Chen, P. Rod Dunbar, Vaughan Feisst, Hilary M. Sheppard, Cris Print |
| المصدر: | Melanoma Research |
| بيانات النشر: | Lippincott Williams & Wilkins, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Pathology, medicine.medical_specialty, Skin Neoplasms, Down-Regulation, Gene Expression, Human skin, Dermatology, Biology, Real-Time Polymerase Chain Reaction, Transfection, cell-to-cell adhesion, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, ANXA2, Gene expression, medicine, melanoma, Humans, RNA, Messenger, Annexin A2, Gene knockdown, Cadherin, Melanoma, Membrane Proteins, medicine.disease, AHNAK, Cadherins, Neoplasm Proteins, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, Oncology, Membrane protein, ORIGINAL ARTICLES: Basic research, 030220 oncology & carcinogenesis, Cancer research, Keratinocyte, cadherin-1 |
| الوصف: | The aim of this study was to further our understanding of the transformation process by identifying differentially expressed proteins in melanocytes compared with melanoma cell lines. Tandem mass spectrometry incorporating iTRAQ reagents was used as a screen to identify and comparatively quantify the expression of proteins in membrane-enriched samples isolated from primary human melanocytes or three melanoma cells lines. Real-time PCR was used to validate significant hits. Immunohistochemistry was used to validate the expression of proteins of interest in melanocytes in human skin and in melanoma-infiltrated lymph nodes. Publically available databases were examined to assess mRNA expression and correlation to patient outcome in a larger cohort of samples. Finally, preliminary functional studies were carried out using siRNAs to reduce the expression of a protein of interest in primary melanocytes and in a keratinocyte cell line. Two proteins, AHNAK and ANXA2, were significantly downregulated in the melanoma cell lines compared with melanocytes. Downregulation was confirmed in tumor cells in a subset of human melanoma-infiltrated human lymph nodes compared with melanocytes in human skin. Examination of Gene Expression Omnibus database data sets suggests that downregulation of AHNAK mRNA and mutation of the AHNAK gene are common in metastatic melanoma and correlates to a poor outcome. Knockdown of AHNAK in primary melanocytes and in a keratinocyte cell line led to a reduction in detectable cadherin-1. This is the first report that we are aware of which correlates a loss of AHNAK with melanoma and poor patient outcome. We hypothesize that AHNAK is required for the expression of functional cadherin-1. |
| اللغة: | English |
| تدمد: | 1473-5636 0960-8931 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8333a36b1d815ba4c04a092711cfc48a http://europepmc.org/articles/PMC4777222 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8333a36b1d815ba4c04a092711cfc48a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14735636 09608931 |
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