title: p38α limits the contribution of MAP17 to cancer progression in breast tumors.
abstract: MAP17 is a small, 17-kDa, non-glycosylated membrane protein that is overexpressed in a percentage of carcinomas. In the present work, we have analyzed the role of MAP17 expression during mammary cancer progression. We have found that MAP17 is expressed in 60% human mammary tumors while it is not expressed in normal or benign neoplasias. MAP17 levels increased with breast tumor stage and were strongly correlated with mammary tumoral progression. A significant increase in the levels of reactive oxygen species (ROS) was observed in MAP17-expressing cells, as compared with parental cells. This increase was further paralleled by an increase in the tumorigenic capacity of carcinoma cells but not in immortal non-tumoral breast epithelial cells, which provides a selective advantage once tumorigenesis has begun. Expression of specific MAP17 shRNA in protein-expressing tumor cells reduced their tumorigenic capabilities, which suggests that this effect is dependent upon MAP17 protein expression. Our data show that ROS functions as a second messenger that enhances tumoral properties, which are inhibited in non-tumoral cells. We have found that p38α activation mediates this response. MAP17 triggers a ROS-dependent, senescence-like response that is abolished in the absence of p38a activation. Furthermore, in human breast tumors, MAP17 activation is correlated with a lack of phosphorylation of p38α. Therefore, MAP17 is overexpressed in late-stage breast tumors, in which oncogenic activity relies on p38 insensitivity to induce intracellular ROS.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Guijarro
authors.forename: M
authors.initials: M
authors.lastname: Vergel
authors.forename: J J
authors.initials: JJ
authors.lastname: Marin
authors.forename: S
authors.initials: S
authors.lastname: Muñoz-Galván
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.forename: S
authors.initials: S
authors.lastname: Ramon y Cajal
authors.forename: G
authors.initials: G
authors.lastname: Roncador
authors.forename: C
authors.initials: C
authors.lastname: Blanco-Aparicio
authors.forename: A
authors.initials: A
authors.lastname: Carnero
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D006801:Humans; D042361:Mammary Glands, Human / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D009857:Oncogenes; D017382:Reactive Oxygen Species / Q000378:metabolism; D046888:Tissue Array Analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C509768:PDZK1IP1 protein, human; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases