title: Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation.
abstract: The exact regulatory mechanisms of carboxyl-terminal modulator protein (CTMP) and its downstream pathways in cancer have been controversial and are not completely understood. Here, we report a new mechanism of regulation of Akt serine/threonine kinase, one of the most important dysregulated signals in head and neck squamous cell carcinoma (HNSCC) by the CTMP pathway and its clinical implications. We find that HNSCC tumor tissues and cell lines had relatively high levels of CTMP expression. Clinical data indicate that CTMP expression was significantly associated with positive lymph node metastasis (OR = 3.8, P = 0.033) and correlated with poor prognosis in patients with HNSCC. CTMP was also positively correlated with Akt/GSK-3β phosphorylation, Snail up-regulation and E-cadherin down-regulation, which lead to increased proliferation and epithelial-to-mesenchymal transition, suggesting that CTMP expression results in enhanced tumorigenic and metastatic properties of HNSCC cells. Moreover, CTMP suppression restores sensitivity to cisplatin chemotherapy. Intriguingly, all the molecular responses to CTMP regulation are identical regardless of p53 status in HNSCC cells. We conclude that CTMP promotes Akt phosphorylation and functions as an oncogenic driver and prognostic marker in HNSCC irrespective of p53.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Seung-Nam
authors.initials: SN
authors.lastname: Jung
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Geun-Ae
authors.initials: GA
authors.lastname: Shim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hee Sung
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.affiliation: Research Institute for Medical Sciences and Pathology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jongsun
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Bon Seok
authors.initials: BS
authors.lastname: Koo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D000071250:Snail Family Transcription Factors; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; C437985:THEM4 protein, human; D013869:Thiolester Hydrolases