title: Involvement of Cot activity in the proliferation of ALCL lymphoma cells.
abstract: Anaplastic large-cell lymphoma (ALCL) cells overexpress CD30 on their cell surface, show increased levels of activated Erk1/2 and of JunB; participating JunB in the proliferative capacity of these lymphomas. Here, we show that ALCL lymphoma cells also present high expression levels of the proto-oncogenic Cot (MAP3K8). Using pharmacological drugs as well as the RNA interference technique we show that Cot protein is responsible for the constitutive Erk1/2 activation in the ALCL lymphoma cells, SUDHL-1. Besides, inhibition of Cot activity reduces the number of cell divisions which is achieved, at least in part, by the control that Cot exercises on the activation state of p70 S6K and on the expression levels of JunB. Since Cot represents an alternative mode, independently of RAF, to activate Erk1/2, all these data strongly suggest that molecular targeting of Cot may be a potential new specific strategy for ALCL lymphomas therapy, without the fully disturbance of the Erk1/2 function.
authors: Instituto de Investigaciones Biomédicas "Alberto Sols", CSIC-UAM, Madrid, Spain. mfernandez@iib.uam.es
authors: Margarita
authors: M
authors: Fernández
authors: Rebeca
authors: R
authors: Manso
authors: Flavia
authors: F
authors: Bernaldo de Quirós
authors: Flavia
authors: F
authors: Bernáldez
authors: Pilar
authors: P
authors: López
authors: Antonio
authors: A
authors: Martín-Duce
authors: Susana
authors: S
authors: Alemany
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D017730:Ki-1 Antigen / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000473:pathology*; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D017730:Ki-1 Antigen; D011518:Proto-Oncogene Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human