title: Could a possible crosstalk between AMPK and TGF-β signaling pathways be a key player in benign and malignant salivary gland tumors?.
abstract: BACKGROUND
  Salivary gland tumors (SGTs) are known for their specific heterogeneity and ambiguous outcome for the affected patients. The LKB1 and SMAD4 genes are pivotal components of important signaling pathways, including AMPK and TGF-β. To our knowledge, no study has reported an association between the expression levels of these genes in SGTs. The expression levels of LKB1 and SMAD4 were evaluated to clarify their possible crosstalk in SGTs.
  
  
  METHODS
  A total of 50 fresh tissue specimens were obtained from patients with SGTs, including pleomorphic adenoma (PA), Warthin's tumor (WT), intermediate grade mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), and carcinoma ex pleomorphic adenoma (CexPA), as well as 8 normal samples. Quantitative real-time polymerase chain reaction was performed for all samples with specific primers.
  
  
  RESULTS
  Data were analyzed using statistical methods. PA, WT, MEC, and SDC showed a significant decrease in LKB1 levels, but the gene was up-regulated in CexPA. SMAD4 was overexpressed in all samples.
  
  
  CONCLUSIONS
  The results suggest a possible link between downregulation of LKB1 and overexpression of SMAD4 in SGTs. LKB1 depletion leads to upregulation of SMAD4, promoting epithelial-mesenchymal transition in tumor cells. Therefore, LKB1 and SMAD4 could be key players in inducing tumor heterogeneity in SGTs.
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Nastaran M
authors.initials: NM
authors.lastname: Ghahhari
authors.forename: Hamed M
authors.initials: HM
authors.lastname: Ghahhari
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kadivar
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020239:Receptor Cross-Talk; D012468:Salivary Gland Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism*; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases