title: Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression.
abstract: 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.
authors.affiliation: Department of Pathology, Affiliated Hospital, Wuxi Medical School, Jiangnan University, Wuxi, China.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: B
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: T
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Endoscopy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China.
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: V
authors.initials: V
authors.lastname: Leventaki
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: E
authors.initials: E
authors.lastname: Drakos
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Experimental Therapeutics Academic Program and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: F X
authors.initials: FX
authors.lastname: Claret
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D000075686:COP9 Signalosome Complex; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex