2026-04-29T16:56:10Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
García-Heredia, José M
author
Verdugo Sivianes, Eva M
author
Lucena-Cacace, Antonio
author
Molina-Pinelo, Sonia
author
Carnero, Amancio
2024-10-23T09:08:09Z
2024-10-23T09:08:09Z
2016
10.18632/oncotarget.11553
1949-2553
Oncotarget
http://hdl.handle.net/10668/10430
27613838
https://hdl.handle.net/20.500.12105/25214
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.
eng
Notch
NumbL
Cancer stem cells
Tumor suppressor
Tumorigenicity
Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like properties and resistance to chemotherapy
research article