| http://purl.uniprot.org/citations/25659576 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25659576 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25659576 | http://www.w3.org/2000/01/rdf-schema#comment | "An inverted pH gradient across the cell membranes is a typical feature of malignant cancer cells that are characterized by extracellular acidosis and cytosol alkalization. These dysregulations are able to create a unique milieu that favors tumor progression, metastasis and chemo/immune-resistance traits of solid tumors. A key event mediating tumor cell pH alterations is an aberrant activation of ion channels and proton pumps such as (H+)-vacuolar-ATPase (V-ATPase). TM9SF4 is a poorly characterized transmembrane protein that we have recently shown to be related to cannibal behavior of metastatic melanoma cells. Here, we demonstrate that TM9SF4 represents a novel V-ATPase-associated protein involved in V-ATPase activation. We have observed in HCT116 and SW480 colon cancer cell lines that TM9SF4 interacts with the ATP6V1H subunit of the V-ATPase V1 sector. Suppression of TM9SF4 with small interfering RNAs strongly reduces assembly of V-ATPase V0/V1 sectors, thus reversing tumor pH gradient with a decrease of cytosolic pH, alkalization of intracellular vesicles and a reduction of extracellular acidity. Such effects are associated with a significant inhibition of the invasive behavior of colon cancer cells and with an increased sensitivity to the cytotoxic effects of 5-fluorouracil. Our study shows for the first time the important role of TM9SF4 in the aberrant constitutive activation of the V-ATPase, and the development of a malignant phenotype, supporting the potential use of TM9SF4 as a target for future anticancer therapies."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2014.437"xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2014.437"xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Matarrese P."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Matarrese P."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Borghi M."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Borghi M."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Bona R."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Bona R."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Venturi G."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Venturi G."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Azzarito T."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Azzarito T."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Canitano A."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Canitano A."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Cara A."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Cara A."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Fais S."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Fais S."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Iessi E."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Iessi E."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Lozupone F."xsd:string |
| http://purl.uniprot.org/citations/25659576 | http://purl.uniprot.org/core/author | "Lozupone F."xsd:string |