Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression. Oncogene 2017 Feb 23;36(8):1069-1079
Date
08/16/2016Pubmed ID
27524414Pubmed Central ID
PMC5311075DOI
10.1038/onc.2016.271Scopus ID
2-s2.0-84982123817 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
Our previous studies demonstrated that Jab1/Csn5 overexpression is correlated with low survival rates in cancer patients, including nasopharyngeal carcinoma (NPC), breast cancer and hepatocellular carcinoma, and contributes to NPC's resistance to radiotherapy and cisplatin by regulating DNA damage and repair pathways. However, the molecular mechanism by which Jab1/Csn5 expression is upregulated in NPCs has yet to be determined. In the present study, we identified the upstream regulator of Jab1/Csn5 expression and demonstrated its role in intrinsic resistance of NPC cells to treatment with cisplatin. Signal transducer and activator of transcription-3 (Stat3) expression correlates with and contributes to Jab1/Csn5 transcription. Consistently, silencing of Stat3 in tumors reduced Jab1/Csn5 expression, thereby sensitizing NPC cells to cisplatin-induced apoptosis both in vitro and in vivo. Mechanistically, Stat3 transcriptionally regulated Jab1/Csn5. Furthermore, high mRNA expression levels of Stat3 or Jab1 in colon cancer, breast cancer and glioblastoma are associated with significantly shorter survival times from the R2 online database. These findings identify a novel Stat3-Jab1/Csn5 signaling axis in cancer pathogenesis with therapeutic and prognostic relevance.
Author List
Pan Y, Wang S, Su B, Zhou F, Zhang R, Xu T, Zhang R, Leventaki V, Drakos E, Liu W, Claret FXMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Animals
Apoptosis
Biomarkers, Tumor
COP9 Signalosome Complex
Carcinoma
Cell Proliferation
Disease Progression
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Inflammation
Intracellular Signaling Peptides and Proteins
Male
Mice
Mice, Nude
Middle Aged
Nasopharyngeal Neoplasms
Neoplasm Staging
Peptide Hydrolases
Prognosis
STAT3 Transcription Factor
Signal Transduction
Transcriptional Activation
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Young Adult