title: TRB3 overexpression due to endoplasmic reticulum stress inhibits AKT kinase activation of tongue squamous cell carcinoma.
abstract: Our investigation aims to evaluate the significance of TRB3, an endoplasmic reticulum stress (ERS)-inducible gene, and explore its relationship with AKT in oral tongue squamous cell carcinoma (OTSCC). Expression of TRB3 and phosphorylated AKT (p-AKT) in OTSCC tissues and adjacent normal tissues were assessed by RT-PCR, Western blot and immunohistochemistry assay. Correlation of TRB3 and AKT was validated by TRB3 adenovirus plasmid (Ad-TRB3) transfection and short hairpin RNA (shRNA) inhibition. The mRNA expression of TRB3 was significantly higher than adjacent noncancerous tissues by RT-PCR in 15 of 18 specimens of OTSCC (83.3%, P<0.01). Both of TRB3 and AKT were highly expressed in 13 of 18 (72.2%) specimens of OTSCC comparing with adjacent noncancerous tissues by Western blot assay (P<0.05). TRB3 was significantly elevated in 49.2% (63/128) of pathologically confirmed specimens and 13.3% (4/30) of adjacent noncancerous specimens by immunohistochemical analysis (P<0.01). TRB3 overexpression was closely correlated with tumor pathological T stage, lymph node metastasis and tumor recurrence. In addition, both mRNA and protein expression of TRB3 was increased under thapsigargin (TG) or tunicmycin (TU)-induced ERS in Tca8113 and CAL-27 cells. Moreover, expression of p-AKT protein decreased when Ad-TRB3 was transected with OTSCC Tca8113 cells. However, expression of p-AKT protein increased when TRB3 was inhibited by TRB3 shRNA inhibition. TRB3 expression was closely correlated with OTSCC prognosis. Under ERS, TRB3 was up-regulated, resulting in inhibiting the activation of AKT in OTSCC.
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Hao-jie
authors.initials: HJ
authors.lastname: Wen
authors.forename: Zhu-ming
authors.initials: ZM
authors.lastname: Guo
authors.forename: Mu-sheng
authors.initials: MS
authors.lastname: Zeng
authors.forename: Man-zhi
authors.initials: MZ
authors.lastname: Li
authors.forename: Yu-e
authors.initials: YE
authors.lastname: Jiang
authors.forename: Xiao-guang
authors.initials: XG
authors.lastname: He
authors.forename: Chuan-zheng
authors.initials: CZ
authors.lastname: Sun
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019284:Thapsigargin / Q000494:pharmacology; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D014415:Tunicamycin; D019284:Thapsigargin; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt