Ebp1 activates podoplanin expression and contributes to oral tumorigenesis

Y. Mei, P. Zhang, H. Zuo, D. Clark, R. Xia, J. Li, Z. Liu, L. Mao

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Podoplanin is highly expressed in human cancers. However, mechanisms regulating podoplanin expression remain elusive. Here we show that podoplanin promotes tumorigenesis of oral squamous cell carcinoma (OSCC) and precancerous cells both in vitro and in vivo, and the ErbB3-binding protein-1 (Ebp1) can be activated in oral tumorigenesis and can serve as a transcriptional activator to drive podoplanin expression in the malignant progression. Most of the OSCC cell lines have no detectable podoplanin protein in low-density cultures. However, the protein becomes detectable in high-density cultures and is required for in-vivo tumor formation of OSCC and oral premalignancies. In a high-density culture condition, podoplanin expression can be triggered at both mRNA and protein levels. In this condition, we showed that Ebp1 is upregulated, translocated from the cytoplasm to the nucleus and binds to the podoplanin promoter to result in a dramatic increase of podoplanin mRNA and protein. Ebp1 downregulation significantly reduced podoplanin expression levels in OSCC cells with a decreased anchorage-dependent growth, invasion and wound healing. Conversely, Ebp1 overexpression enhanced these malignant features through podoplanin upregulation both in vitro and in vivo. In 81 patients with oral premalignant lesions, we found that Ebp1 expression is strongly related to OSCC development. We conclude that Ebp1 has a key role in the upregulation of podoplanin and may contribute to oral tumorigenesis.

Original languageEnglish (US)
Pages (from-to)3839-3850
Number of pages12
JournalOncogene
Volume33
Issue number29
DOIs
StatePublished - Jul 17 2014

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Carrier Proteins
Carcinogenesis
Squamous Cell Carcinoma
Proteins
Up-Regulation
Messenger RNA
Wound Healing
Neoplasms
Cytoplasm
Down-Regulation
Cell Line
Growth
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Mei, Y., Zhang, P., Zuo, H., Clark, D., Xia, R., Li, J., ... Mao, L. (2014). Ebp1 activates podoplanin expression and contributes to oral tumorigenesis. Oncogene, 33(29), 3839-3850. https://doi.org/10.1038/onc.2013.354
Mei, Y. ; Zhang, P. ; Zuo, H. ; Clark, D. ; Xia, R. ; Li, J. ; Liu, Z. ; Mao, L. / Ebp1 activates podoplanin expression and contributes to oral tumorigenesis. In: Oncogene. 2014 ; Vol. 33, No. 29. pp. 3839-3850.
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Mei, Y, Zhang, P, Zuo, H, Clark, D, Xia, R, Li, J, Liu, Z & Mao, L 2014, 'Ebp1 activates podoplanin expression and contributes to oral tumorigenesis', Oncogene, vol. 33, no. 29, pp. 3839-3850. https://doi.org/10.1038/onc.2013.354

Ebp1 activates podoplanin expression and contributes to oral tumorigenesis. / Mei, Y.; Zhang, P.; Zuo, H.; Clark, D.; Xia, R.; Li, J.; Liu, Z.; Mao, L.

In: Oncogene, Vol. 33, No. 29, 17.07.2014, p. 3839-3850.

Research output: Contribution to journalArticle

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Mei Y, Zhang P, Zuo H, Clark D, Xia R, Li J et al. Ebp1 activates podoplanin expression and contributes to oral tumorigenesis. Oncogene. 2014 Jul 17;33(29):3839-3850. https://doi.org/10.1038/onc.2013.354