Low disabled-2 expression promotes tumor progression and determines poor survival and high recurrence of esophageal squamous cell carcinoma

Wen Lun Wang, Wei Lun Chang, Hsiao Bai Yang, Yu Chi Wang, I. Wei Chang, Ching Tai Lee, Chi Yang Chang, Jaw Town Lin, Bor Shyang Sheu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and high recurrence rate, but lack a prognostic biomarker. Disabled-2 (DAB2) is a crucial tumor suppressor, but its roles in ESCCs are uncertain. We investigated whether low DAB2 expression in ESCCs could lead into tumor progression and poor prognosis. Our results found patients with low-DAB2 expression ESCCs had significantly larger tumor size, deeper tumor invasion depth, lymph node metastasis, worse survival, and higher recurrence rate (P<0.05). The Cox-regression model revealed low-DAB2 expression was an independent factor of poor survival (P<0.05), and also of tumor recurrence with the predictive performance superior to clinical TNM stage (P<0.05). Low-DAB2 cancer cells, validated by DAB2 knockdown or overexpression, had higher phosphorylated ERK and migration abilities, which could be suppressed by ERK inhibitor treatment. TGF-β-induced epithelial-to-mesenchymal transition (EMT) only existed in the high-DAB2 cells, and related to worse prognosis of high-DAB2 ESCCs (P<0.05). In conclusion, DAB2 can suppress the ERK signaling, but correlate to have TGF-β-induced EMT in ESCCs. DAB2 expression could be a biomarker to identify patients with worse survival and high recurrence. Our data suggest DAB2 expression can stratify patients in need of aggressive surveillance and with possible benefit from anti-ERK or anti-TGF-β therapies.

Original languageEnglish
Pages (from-to)71169-71181
Number of pages13
JournalOncotarget
Volume7
Issue number44
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

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Keywords

  • Disabled-2
  • Esophageal cancer
  • Recurrence
  • Survival

ASJC Scopus subject areas

  • Oncology

Cite this

Wang, W. L., Chang, W. L., Yang, H. B., Wang, Y. C., Chang, I. W., Lee, C. T., Chang, C. Y., Lin, J. T., & Sheu, B. S. (2016). Low disabled-2 expression promotes tumor progression and determines poor survival and high recurrence of esophageal squamous cell carcinoma. Oncotarget, 7(44), 71169-71181. https://doi.org/10.18632/oncotarget.8460