Transforming growth factor-β1 activates ΔNp63/c-Myc to promote oral squamous cell carcinoma

Lihua Hu, Jingpeng Liu, Zhi Li, Chunling Wang, Ali Nawshad

Research output: Contribution to journalArticle

5 Scopus citations

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. Study Design 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.

Original languageEnglish (US)
Pages (from-to)460-482.e4
JournalOral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Volume122
Issue number4
DOIs
Publication statusPublished - Oct 1 2016

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ASJC Scopus subject areas

  • Surgery
  • Oral Surgery
  • Pathology and Forensic Medicine
  • Dentistry (miscellaneous)
  • Radiology Nuclear Medicine and imaging

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