Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like
properties and resistance to chemotherapy
#MMPMID27613838
García-Heredia JM
; Verdugo Sivianes EM
; Lucena-Cacace A
; Molina-Pinelo S
; Carnero A
Oncotarget
2016[Sep]; 7
(39
): 63611-63628
PMID27613838
show ga
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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