title: Transforming growth factor-β1 activates ΔNp63/c-Myc to promote oral squamous cell carcinoma.
abstract: OBJECTIVE
  During the development of oral squamous cell carcinoma (OSCC), the transformed epithelial cells undergo increased proliferation resulting in tumor growth and invasion. Interestingly, throughout all phases of differentiation and progression to OSCC, transforming growth factor-β1 (TGF)-β1 induces cell cycle arrest or apoptosis; however, the role of TGF-β1 in promoting cancer cell proliferation has not been explored in detail. The purpose of this study was to identify the effect of TGF-β1 on OSCC cell proliferation.
  
  
  METHODS
  Using both human OSCC samples and cell lines (UMSCC38 and UMSCC11B), we assessed protein, mRNA, gene expression, and protein-DNA interactions during OSCC progression.
  
  
  RESULTS
  Our results showed that TGF-β1 increased OSCC cell proliferation by upregulating the expression of ΔNp63 and c-Myc oncogenes. Although the basal OSCC cell proliferation is sustained by activating ΔNp63, increased induction of c-Myc causes unregulated OSCC cell proliferation. Following induction of the cell cycle by ΔNp63 and c-Myc, cancer cells that halt c-Myc activity undergo epithelial mesenchymal transition or invasion while those that continue to express ΔNp63/c-Myc undergo unlimited progression through the cell cycle.
  
  
  CONCLUSIONS
  OSCC proliferation is manifested by the induction of c-Myc in response to TGF-β1 signaling, which is essential for OSCC growth. Our data highlight the potential role of TGF-β1 in the induction of cancer progression and invasion of OSCC.
authors: Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE, USA; Shandong Provincial Key Laboratory of Oral Biomedicine, Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong, P.R. China.
authors: Lihua
authors: L
authors: Hu
authors: Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE, USA.
authors: Jingpeng
authors: J
authors: Liu
authors: Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE, USA.
authors: Zhi
authors: Z
authors: Li
authors: Shandong Provincial Key Laboratory of Oral Biomedicine, Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong, P.R. China.
authors: Chunling
authors: C
authors: Wang
authors: Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE, USA. Electronic address: Anawshad@unmc.edu.
authors: Ali
authors: A
authors: Nawshad
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005434:Flow Cytometry; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D060787:Neoplasm Grading; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C115051:TP63 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins