Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like properties and resistance to chemotherapy
NumbL, or Numb-like, is a close homologue of Numb, and is part of an evolutionary conserved protein family implicated in some important cellular processes. Numb is a protein involved in cell development, in cell adhesion and migration, in asymmetric cell division, and in targeting proteins for endoc...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/25214 |
| Acceso en línea: | https://hdl.handle.net/20.500.12105/25214 |
| Access Level: | acceso abierto |
| Palabra clave: | Notch NumbL Cancer stem cells Tumor suppressor Tumorigenicity Active Transport, Cell Nucleus Animals Antineoplastic Agents Breast Neoplasms Carcinogenesis Cell Adhesion Cell Line, Tumor Cell Movement Colorectal Neoplasms Dose-Response Relationship, Drug Down-Regulation Drug Resistance, Neoplasm Endocytosis Epithelial-Mesenchymal Transition Female Gene Expression Regulation, Neoplastic HeLa Cells Humans Intracellular Signaling Peptides and Proteins Lung Neoplasms Mice Neoplastic Stem Cells Receptors, Notch Sarcoma |
| Sumario: | NumbL, or Numb-like, is a close homologue of Numb, and is part of an evolutionary conserved protein family implicated in some important cellular processes. Numb is a protein involved in cell development, in cell adhesion and migration, in asymmetric cell division, and in targeting proteins for endocytosis and ubiquitination. NumbL exhibits some overlapping functions with Numb, but its role in tumorigenesis is not fully known. Here we showed that the downregulation of NumbL alone is sufficient to increase NICD nuclear translocation and induce Notch pathway activation. Furthermore, NumbL downregulation increases epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-related gene transcripts and CSC-like phenotypes, including an increase in the CSC-like pool. These data suggest that NumbL can act independently as a tumor suppressor gene. Furthermore, an absence of NumbL induces chemoresistance in tumor cells. An analysis of human tumors indicates that NumbL is downregulated in a variable percentage of human tumors, with lower levels of this gene correlated with worse prognosis in colon, breast and lung tumors. Therefore, NumbL can act as an independent tumor suppressor inhibiting the Notch pathway and regulating the cancer stem cell pool. |
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