TY - JOUR
T1 - NF-kappa B-inducing kinase regulates stem cell phenotype in breast cancer
AU - Vazquez-Santillan, Karla
AU - Melendez-Zajgla, Jorge
AU - Jimenez-Hernandez, Luis Enrique
AU - Gaytan-Cervantes, Javier
AU - Munõz-Galindo, Laura
AU - Pinã-Sanchez, Patricia
AU - Martinez-Ruiz, Gustavo
AU - Torres, Javier
AU - Garcia-Lopez, Patricia
AU - Gonzalez-Torres, Carolina
AU - Ruiz, Victor
AU - Avila-Moreno, Federico
AU - Velasco-Velazquez, Marco
AU - Perez-Tapia, Mayra
AU - Maldonado, Vilma
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/11/23
Y1 - 2016/11/23
N2 - Breast cancer stem cells (BCSCs) overexpress components of the Nuclear factor-kappa B (NF-ΰ B) signaling cascade and consequently display high NF-κB activity levels. Breast cancer cell lines with high proportion of CSCs exhibit high NF-κB-inducing kinase (NIK) expression. The role of NIK in the phenotype of cancer stem cell regulation is poorly understood. Expression of NIK was analyzed by quantitative RT-PCR in BCSCs. NIK levels were manipulated through transfection of specific shRNAs or an expression vector. The effect of NIK in the cancer stem cell properties was assessed by mammosphere formation, mice xenografts and stem markers expression. BCSCs expressed higher levels of NIK and its inhibition through small hairpin (shRNA), reduced the expression of CSC markers and impaired clonogenicity and tumorigenesis. Genome-wide expression analyses suggested that NIK acts on ERK1/2 pathway to exert its activity. In addition, forced expression of NIK increased the BCSC population and enhanced breast cancer cell tumorigenicity. The in vivo relevance of these results is further supported by a tissue microarray of breast cancer samples in which we observed correlated expression of Aldehyde dehydrogenase (ALDH) and NIK protein. Our results support the essential involvement of NIK in BCSC phenotypic regulation via ERK1/2 and NF-κB.
AB - Breast cancer stem cells (BCSCs) overexpress components of the Nuclear factor-kappa B (NF-ΰ B) signaling cascade and consequently display high NF-κB activity levels. Breast cancer cell lines with high proportion of CSCs exhibit high NF-κB-inducing kinase (NIK) expression. The role of NIK in the phenotype of cancer stem cell regulation is poorly understood. Expression of NIK was analyzed by quantitative RT-PCR in BCSCs. NIK levels were manipulated through transfection of specific shRNAs or an expression vector. The effect of NIK in the cancer stem cell properties was assessed by mammosphere formation, mice xenografts and stem markers expression. BCSCs expressed higher levels of NIK and its inhibition through small hairpin (shRNA), reduced the expression of CSC markers and impaired clonogenicity and tumorigenesis. Genome-wide expression analyses suggested that NIK acts on ERK1/2 pathway to exert its activity. In addition, forced expression of NIK increased the BCSC population and enhanced breast cancer cell tumorigenicity. The in vivo relevance of these results is further supported by a tissue microarray of breast cancer samples in which we observed correlated expression of Aldehyde dehydrogenase (ALDH) and NIK protein. Our results support the essential involvement of NIK in BCSC phenotypic regulation via ERK1/2 and NF-κB.
UR - http://www.scopus.com/inward/record.url?scp=84997386090&partnerID=8YFLogxK
U2 - 10.1038/srep37340
DO - 10.1038/srep37340
M3 - Artículo
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 37340
ER -