Aberrant expression of a β-catenin gain-of-function mutant induces hyperplastic transformation in the mouse cornea

Yujin Zhang, Mindy K. Call, Lung Kun Yeh, Hongshan Liu, Tyler Kochel, I. Jong Wang, Pao Hsien Chu, Makoto M. Taketo, James V. Jester, Winston W.Y. Kao, Chia Yang Liu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

22 Scopus citations


β-catenin signaling has been shown to play a fundamental role in embryonic development and tumorigenesis. In this study, we investigated the role of β-catenin (Ctnnb1) in corneal homeostasis and tumorigenesis. Conditional expression of a murine Ctnnb1 gain-of-function mutation alone caused corneal neoplasia and neovascularization, resembling human ocular surface squamous neoplasia (OSSN). These corneas displayed an upregulation of cell proliferative markers (PCNA and p63), while presenting downregulation of both the Pax-6 transcription factor and the corneal differentiation marker cytokeratin 12. In addition, the expression of limbal-type keratin 15 ectopically extended to cornea, but the pattern of conjunctival keratin 4 and epidermal keratin 10 were unchanged. Moreover, epithelial E-cadherin and laminins decreased concomitantly with elevated levels of MMP-7. We also noticed a dramatic upregulation of pro-angiogenic factors (Vegf-A, Vegfr1) and angiopoietins in these corneas. Interestingly, all human OSSN specimens examined revealed nuclear β-catenin immunoreactivity. Taken together, these results argue that β-catenin activation is a crucial step during OSSN pathogenesis. Thus, inhibition of β-catenin might be beneficial for treating this disease.

Original languageEnglish
Pages (from-to)1285-1294
Number of pages10
JournalJournal of Cell Science
Issue number8
StatePublished - 15 04 2010
Externally publishedYes


  • Corneal epithelium
  • OSSN
  • Tumorigenesis
  • β-catenin


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