دورية أكاديمية
Golgi tethering factor golgin-97 suppresses breast cancer cell invasiveness by modulating NF-κB activity
العنوان: | Golgi tethering factor golgin-97 suppresses breast cancer cell invasiveness by modulating NF-κB activity |
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المؤلفون: | Rae-Mann Hsu, Cai-Yan Zhong, Chih-Liang Wang, Wei-Chao Liao, Chi Yang, Shih-Yu Lin, Jia-Wei Lin, Hsiao-Yun Cheng, Po-Yu Li, Chia-Jung Yu |
المصدر: | Cell Communication and Signaling, Vol 16, Iss 1, Pp 1-17 (2018) |
بيانات النشر: | BMC, 2018. |
سنة النشر: | 2018 |
المجموعة: | LCC:Medicine LCC:Cytology |
مصطلحات موضوعية: | Golgin-97, TGN, Golgi apparatus, Cell migration, NF-κB, Breast cancer, Medicine, Cytology, QH573-671 |
الوصف: | 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. 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). 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. 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1478-811X |
Relation: | http://link.springer.com/article/10.1186/s12964-018-0230-5; https://doaj.org/toc/1478-811X |
DOI: | 10.1186/s12964-018-0230-5 |
URL الوصول: | https://doaj.org/article/2f2c537cfbad4950b819558bdd9eab33 |
رقم الأكسشن: | edsdoj.2f2c537cfbad4950b819558bdd9eab33 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 1478811X |
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DOI: | 10.1186/s12964-018-0230-5 |