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Golgi tethering factor golgin-97 suppresses breast cancer cell invasiveness by modulating NF-κB activity.
- Source :
-
Cell communication and signaling : CCS [Cell Commun Signal] 2018 Apr 27; Vol. 16 (1), pp. 19. Date of Electronic Publication: 2018 Apr 27. - Publication Year :
- 2018
-
Abstract
- Background: Golgin-97 is a tethering factor in the trans-Golgi network (TGN) and is crucial for vesicular trafficking and maintaining cell polarity. However, the significance of golgin-97 in human diseases such as cancer remains unclear.<br />Methods: We searched for a potential role of golgin-97 in cancers using Kaplan-Meier Plotter ( http://kmplot.com ) and Oncomine ( www.oncomine.org ) datasets. Specific functions of golgin-97 in migration and invasion were examined in golgin-97-knockdown and golgin-97-overexpressing cells. cDNA microarray, pathway analysis and qPCR were used to identify gene profiles regulated by golgin-97. The role of golgin-97 in NF-κB signaling pathway was examined by using subcellular fractionation, luciferase reporter assay, western blot analysis and immunofluorescence assay (IFA).<br />Results: We found that low expression of golgin-97 correlated with poor overall survival of cancer patients and was associated with invasiveness in breast cancer cells. Golgin-97 knockdown promoted cell migration and invasion, whereas re-expression of golgin-97 restored the above phenotypes in breast cancer cells. Microarray and pathway analyses revealed that golgin-97 knockdown induced the expression of several invasion-promoting genes that were transcriptionally regulated by NF-κB p65. Mechanistically, golgin-97 knockdown significantly reduced IκBα protein levels and activated NF-κB, whereas neither IκBα levels nor NF-κB activity was changed in TGN46- or GCC185-knockdown cells. Conversely, golgin-97 overexpression suppressed NF-κB activity and restored the levels of IκBα in golgin-97-knockdown cells. Interestingly, the results of Golgi-disturbing agent treatment revealed that the loss of Golgi integrity was not involved in the NF-κB activation induced by golgin-97 knockdown. Moreover, both TGN-bound and cytosolic golgin-97 inhibited NF-κB activation, indicating that golgin-97 functions as an NF-κB suppressor regardless of its subcellular localization.<br />Conclusion: Our results collectively demonstrate a novel and suppressive role of golgin-97 in cancer invasiveness. We also provide a new avenue for exploring the relationship between the TGN, golgin-97 and NF-κB signaling in tumor progression.
- Subjects :
- Autoantigens genetics
Breast Neoplasms metabolism
Breast Neoplasms mortality
Cell Line, Tumor
Cell Movement
Databases, Factual
Female
Golgi Matrix Proteins antagonists & inhibitors
Golgi Matrix Proteins genetics
Humans
Kaplan-Meier Estimate
Membrane Glycoproteins metabolism
NF-KappaB Inhibitor alpha metabolism
Phosphorylation
Prognosis
RNA Interference
RNA, Small Interfering metabolism
Signal Transduction
Transcription Factor RelA metabolism
Autoantigens metabolism
Breast Neoplasms pathology
Golgi Matrix Proteins metabolism
NF-kappa B metabolism
trans-Golgi Network metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1478-811X
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell communication and signaling : CCS
- Publication Type :
- Academic Journal
- Accession number :
- 29703230
- Full Text :
- https://doi.org/10.1186/s12964-018-0230-5