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Cell survival and protein secretion associated with Golgi integrity in response to Golgi stress‐inducing agents
Author(s) -
Ignashkova Tatiana I.,
Gendarme Mathieu,
Peschk Katrin,
Eggenweiler HansMichael,
Lindemann Ralph K.,
Reiling Jan H.
Publication year - 2017
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12493
Subject(s) - brefeldin a , golgi apparatus , microbiology and biotechnology , endoplasmic reticulum , biology , secretion , secretory pathway , endosome , unfolded protein response , biochemistry , intracellular
The Golgi apparatus is part of the secretory pathway and of central importance for modification, transport and sorting of proteins and lipids. ADP ‐ribosylation factors, whose activation can be blocked by brefeldin A ( BFA ), play a major role in functioning of the Golgi network and regulation of membrane traffic and are also involved in proliferation and migration of cancer cells. Due to high cytotoxicity and poor bioavailability, BFA has not passed the preclinical stage of drug development. Recently, AMF‐26 and golgicide A have been described as novel inhibitors of the Golgi system with antitumor or bactericidal properties. We provide here further evidence that AMF‐26 closely mirrors the mode of action of BFA but is less potent. Using several human cancer cell lines, we studied the effects of AMF‐26 , BFA and golgicide A on cell homeostasis including Golgi structure, endoplasmic reticulum (ER) stress markers, secretion and viability, and found overall a significant correlation between these parameters. Furthermore, modulation of ADP ‐ribosylation factor expression has a profound impact on Golgi organization and survival in response to Golgi stress inducers.