Ectopic expression of the heterotrimeric G15 protein in pancreatic carcinoma and its potential in cancer signal transduction

Francesco Giovinazzo, Giorgio Malpeli, Sara Zanini, Marco Parenti, Lorenzo Piemonti, Marco Colombatti, Maria Teresa Valenti, Luca Dalle Carbonare, Aldo Scarpa, James Sinnett-Smith, Enrique Rozengurt, Claudio Bassi, Giulio Innamorati

Research output: Contribution to journalArticle

Abstract

G15 is a heterotrimeric G protein selectively expressed in immature cell lineages in adult tissues that feature higher cell renewal potential. It promiscuously couples a wide variety of G protein-coupled receptors (GPCRs) to phospholipase C. Intriguingly, G15 is poorly affected by GPCR desensitization. We show here that G15 α-subunit (Gα15) supports sustained stimulation of PKD1 by a constitutively desensitized GPCR co-transfected over a negative cell background.Based on the fact that PKD1 is a multifunctional protein kinase activated by PKC and known for promoting oncogenic signaling, we hypothesized that, if expressed out of its natural cell context, G15 might promote tumor growth. A screening for Gα15 mRNA expression pointed to pancreatic carcinoma among different human cancer cell types and revealed significant expression in human tumor biopsies xenografted in mice.In addition, G15 ectopic presence could functionally contribute to the transformation process since siRNA-induced depletion of Gα15 in pancreatic carcinoma cell lines dramatically inhibited anchorage-independent growth and resistance to the lack of nutrients.Altogether, our findings suggest that G15 supports tumorigenic signaling in pancreas and hence it may be considered as a novel potential target for the therapy of this form of cancer.

Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalCellular Signalling
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2013

Keywords

  • G15
  • Heterotrimeric G proteins
  • Pancreatic carcinoma

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Giovinazzo, F., Malpeli, G., Zanini, S., Parenti, M., Piemonti, L., Colombatti, M., Valenti, M. T., Carbonare, L. D., Scarpa, A., Sinnett-Smith, J., Rozengurt, E., Bassi, C., & Innamorati, G. (2013). Ectopic expression of the heterotrimeric G15 protein in pancreatic carcinoma and its potential in cancer signal transduction. Cellular Signalling, 25(3), 651-659. https://doi.org/10.1016/j.cellsig.2012.11.018