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Sci Rep. 2016 Jun 22;6:28503. doi: 10.1038/srep28503.

Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation.

Author information

  • 1Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University, Daejeon, Republic of Korea.
  • 2Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • 3Research Institute for Medical Sciences and Pathology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • 4Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

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.

PMID:
27328758
PMCID:
PMC4916413
DOI:
10.1038/srep28503
[PubMed - in process]
Free PMC Article
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