Nature communications, 2020-01, Vol.11 (1), p.333-18, Article 333
- Marie, Kerrie L.
- Sassano, Antonella
- Yang, Howard H.
- Michalowski, Aleksandra M.
- Michael, Helen T.
- Guo, Theresa
- Tsai, Yien Che
- Weissman, Allan M.
- Lee, Maxwell P.
- Jenkins, Lisa M.
- Zaidi, M. Raza
- Pérez-Guijarro, Eva
- Day, Chi-Ping
- Ylaya, Kris
- Hewitt, Stephen M.
- Patel, Nimit L.
- Arnheiter, Heinz
- Davis, Sean
- Meltzer, Paul S.
- Merlino, Glenn
- Mishra, Pravin J.
2020
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- Autor(en) / Beteiligte
- Marie, Kerrie L.
- Sassano, Antonella
- Yang, Howard H.
- Michalowski, Aleksandra M.
- Michael, Helen T.
- Guo, Theresa
- Tsai, Yien Che
- Weissman, Allan M.
- Lee, Maxwell P.
- Jenkins, Lisa M.
- Zaidi, M. Raza
- Pérez-Guijarro, Eva
- Day, Chi-Ping
- Ylaya, Kris
- Hewitt, Stephen M.
- Patel, Nimit L.
- Arnheiter, Heinz
- Davis, Sean
- Meltzer, Paul S.
- Merlino, Glenn
- Mishra, Pravin J.
- Titel
- Melanoblast transcriptome analysis reveals pathways promoting melanoma metastasis
- Ist Teil von
- Nature communications, 2020-01, Vol.11 (1), p.333-18, Article 333
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2020
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- Cutaneous malignant melanoma is an aggressive cancer of melanocytes with a strong propensity to metastasize. We posit that melanoma cells acquire metastatic capability by adopting an embryonic-like phenotype, and that a lineage approach would uncover metastatic melanoma biology. Using a genetically engineered mouse model to generate a rich melanoblast transcriptome dataset, we identify melanoblast-specific genes whose expression contribute to metastatic competence and derive a 43-gene signature that predicts patient survival. We identify a melanoblast gene, KDELR3 , whose loss impairs experimental metastasis. In contrast, KDELR1 deficiency enhances metastasis, providing the first example of different disease etiologies within the KDELR-family of retrograde transporters. We show that KDELR3 regulates the metastasis suppressor, KAI1, and report an interaction with the E3 ubiquitin-protein ligase gp78, a regulator of KAI1 degradation. Our work demonstrates that the melanoblast transcriptome can be mined to uncover targetable pathways for melanoma therapy. Metastatic cells can mimic many of the phenotypic behaviors of embryonic cells. Here, the authors generate a melanoblast-specific transcriptome using a genetically engineered mouse model and identify KDELR3 as a pro-metastasis gene in melanoma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-14085-2Titel-ID: cdi_doaj_primary_oai_doaj_org_article_35727847607f4f45b98d5dc601c357f5
- Format
- –
- Schlagworte
- 13/31, 13/51, 14/1, 14/63, 38/39, 38/61, 38/77, 38/90, 38/91, 42/89, 49/109, 631/67/1813/1634, 631/67/322, 631/80/304, 631/80/470/1463, 64, 64/60, 82/58, Animals, Cell Line, Tumor, Endoplasmic Reticulum, Etiology, Female, Gene expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Genetic engineering, Humanities and Social Sciences, Humans, Kangai-1 Protein - genetics, Kangai-1 Protein - metabolism, Lung - pathology, Melanocytes, Melanocytes - metabolism, Melanoma, Melanoma - genetics, Melanoma - metabolism, Melanoma - pathology, Melanoma, Cutaneous Malignant, Metastases, Metastasis, Mice, Mice, Inbred C57BL, multidisciplinary, Neoplasm Metastasis - genetics, Neoplasms, Second Primary - pathology, Phenotype, Phenotypes, Receptors, Peptide - genetics, Receptors, Peptide - metabolism, Science, Science (multidisciplinary), Skin cancer, Skin Neoplasms - genetics, Skin Neoplasms - metabolism, Skin Neoplasms - pathology, Transcriptome, Ubiquitin, Ubiquitin-protein ligase, Ubiquitin-Protein Ligases - metabolism