2026-04-29T16:56:09Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/252142024-10-23T09:08:09Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16938col_20.500.12105_16927

00925njm 22002777a 4500 dc García-Heredia, José M author Verdugo Sivianes, Eva M author Lucena-Cacace, Antonio author Molina-Pinelo, Sonia author Carnero, Amancio author 2016 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. 10.18632/oncotarget.11553 1949-2553 Oncotarget http://hdl.handle.net/10668/10430 27613838 https://hdl.handle.net/20.500.12105/25214 Notch NumbL Cancer stem cells Tumor suppressor Tumorigenicity Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like properties and resistance to chemotherapy