A Golgi-based KDELR-dependent signalling pathway controls extracellular matrix degradation

Carmen Ruggiero, Giorgia Fragassi, Mauro Grossi, Benedetta Picciani, Rosaria Di Martino, Mirco Capitani, Roberto Buccione, Alberto Luini, Michele Sallese

Research output: Contribution to journalArticle

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 KDELRacts 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.

Original languageEnglish
Pages (from-to)3375-3393
Number of pages19
JournalOncotarget
Volume6
Issue number5
Publication statusPublished - 2015

Keywords

  • Cancer cell invasion
  • Cell signalling
  • Src family kinases

ASJC Scopus subject areas

  • Oncology

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    Ruggiero, C., Fragassi, G., Grossi, M., Picciani, B., Di Martino, R., Capitani, M., Buccione, R., Luini, A., & Sallese, M. (2015). A Golgi-based KDELR-dependent signalling pathway controls extracellular matrix degradation. Oncotarget, 6(5), 3375-3393.