Article
Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like properties and resistance to chemotherapy
Author/s | García Heredia, José Manuel
Verdugo Sivianes, Eva María Lucena Cacace, Antonio Molina Pinelo, Sonia Carnero Moya, Amancio |
Department | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Publication Date | 2016 |
Deposit Date | 2017-04-26 |
Published in |
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Abstract | 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 ... 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. |
Project ID. | PI12/00137
PI15/00045 CTS-6844 CTS-1848 PI-0306-2012 PI-0096-2014 |
Citation | García Heredia, J.M., Verdugo Sivianes, E.M., Lucena Cacace, A., Molina Pinelo, S. y Carnero, A. (2016). Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like properties and resistance to chemotherapy. Oncotarget, 7 (39), 63611-63628. |
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