title: A Golgi-based KDELR-dependent signalling pathway controls extracellular matrix degradation.
abstract: We recently identified an endomembrane-based signalling cascade that is activated by the KDEL receptor (KDELR) on the Golgi complex. At the Golgi, the KDELR acts as a traffic sensor (presumably via binding to chaperones that leave the ER) and triggers signalling pathways that balance membrane fluxes between ER and Golgi. One such pathway relies on Gq and Src. Here, we examine if KDELR might control other cellular modules through this pathway. Given the central role of Src in extracellular matrix (ECM) degradation, we investigated the impact of the KDELR-Src pathway on the ability of cancer cells to degrade the ECM. We find that activation of the KDELR controls ECM degradation by increasing the number of the degradative structures known as invadopodia. The KDELR induces Src activation at the invadopodia and leads to phosphorylation of the Src substrates cortactin and ASAP1, which are required for basal and KDELR-stimulated ECM degradation. This study furthers our understanding of the regulatory circuitry underlying invadopodia-dependent ECM degradation, a key phase in metastases formation and invasive growth.
authors: Unit of Genomic Approaches to Membrane Traffic, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.|Current address: Institut de Pharmacologie Moléculaire et Cellulaire CNRS and Associated International Laboratory (LIA) NEOGENEX CNRS and University of Nice-Sophia-Antipolis, Valbonne, France.
authors: Carmen
authors: C
authors: Ruggiero
authors: Unit of Genomic Approaches to Membrane Traffic, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Giorgia
authors: G
authors: Fragassi
authors: Unit of Genomic Approaches to Membrane Traffic, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Mauro
authors: M
authors: Grossi
authors: Unit of Genomic Approaches to Membrane Traffic, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Benedetta
authors: B
authors: Picciani
authors: Institute of Protein Biochemistry National Research Council, Naples, Italy.
authors: Rosaria
authors: R
authors: Di Martino
authors: Unit of Genomic Approaches to Membrane Traffic, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Mirco
authors: M
authors: Capitani
authors: Laboratory of Tumour Cell Invasion, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Roberto
authors: R
authors: Buccione
authors: Institute of Protein Biochemistry National Research Council, Naples, Italy.
authors: Alberto
authors: A
authors: Luini
authors: Unit of Genomic Approaches to Membrane Traffic, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Michele
authors: M
authors: Sallese
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D051356:Cortactin / Q000378:metabolism; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D000069261:Podosomes / Q000378:metabolism; D034622:RNA Interference; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C117891:ASAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C495868:CTTN protein, human; D051356:Cortactin; C489304:KDELR1 protein, human; D018000:Receptors, Peptide; D033921:Vesicular Transport Proteins; C074642:KDELR2 protein, human; D019061:src-Family Kinases