IGF-1 drives chromogranin A secretion via activation of Arf1 in human neuroendocrine tumour cells

Journal of Cellular and Molecular Medicine
Christin MünzbergGötz von Wichert

Abstract

Hypersecretion is the major symptom of functional neuroendocrine tumours. The mechanisms that contribute to this excessive secretion of hormones are still elusive. A key event in secretion is the exit of secretory products from the Golgi apparatus. ADP-ribosylation factor (Arf) GTPases are known to control vesicle budding and trafficking, and have a leading function in the regulation of formation of secretory granula at the Golgi. Here, we show that Arf1 is the predominant Arf protein family member expressed in the neuroendocrine pancreatic tumour cell lines BON and QGP-1. In BON cells Arf1 colocalizes with Golgi markers as well as chromogranin A, and shows significant basal activity. The inhibition of Arf1 activity or expression significantly impaired secretion of chromogranin A. Furthermore, we show that the insulin-like growth factor 1 (IGF-1), a major regulator of growth and secretion in BON cells, induces Arf1 activity. We found that activation of Arf1 upon IGF-1 receptor stimulation is mediated by MEK/ERK signalling pathway in BON and QGP-1 cells. Moreover, the activity of Arf1 in BON cells is mediated by autocrinely secreted IGF-1, and concomitantly, autocrine IGF1 secretion is maintained by Arf1 activity. In summary, ou...Continue Reading

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Citations

Mar 27, 2007·Best Practice & Research. Clinical Endocrinology & Metabolism·James C Yao
Jun 6, 2007·Hematology/oncology Clinics of North America·James C Yao, Paulo M Hoff
Jun 21, 2017·Cellular Oncology (Dordrecht)·Concha López-GinésMiguel Cerdá-Nicolás
Aug 16, 2017·Journal of Cell Science·Alexander BecherThomas Seufferlein

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Methods Mentioned

BETA
GTPases
nucleotide exchange
Transfection
PCR
transfections
pull-down
ELISA
confocal microscopy
fluorescence microscopy
electron microscopy

Software Mentioned

GraphPad Prism
GraphPad

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