Tumor suppressor dual-specificity phosphatase 6 (DUSP6) impairs cell invasion and epithelial-mesenchymal transition (EMT)-associated phenotype

Victor Chun Lam Wong, Han Chen, Josephine Mun Yee Ko, Kwok Wah Chan, Yuen Piu Chan, Simon Law, Daniel Chua, Dora Lai Wan Kwong, Hong Lok Lung, Gopesh Srivastava, Cheuk On Tang, Sai Wah Tsao, Eugene R. Zabarovsky, Eric J. Stanbridge, Maria Li Lung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

60 Citations (Scopus)

Abstract

Suppressive effects of DUSP6 in tumorigenesis and EMT-associated properties were observed. Dual-specificity phosphatase (DUSP6) is a MAP kinase phosphatase (MKP) negatively regulating the activity of ERK, one of the major molecular switches in the MAPK signaling cascade propagating the signaling responses during malignancies. The impact of DUSP6 in EMT and its contribution to tumor dissemination has not yet been characterized. Due to differences in tumor microenvironments affecting cell signaling during cancer progression, DUSP6 may play varying roles in tumor development. We sought to examine the potential role of DUSP6-mediated tumorigenesis and EMT-associated properties in two aerodigestive tract cancers, namely, esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). Significant loss of DUSP6 was observed in 100% of 11 ESCC cell lines and 71% of seven NPC cell lines. DUSP6 expression was down-regulated in 40% of 30 ESCC tumor tissues and 75% of 20 NPC tumor tissues compared to their respective normal counterparts. Suppressive effects of DUSP6 in tumor formation and cancer cell mobility are seen in in vivo tumorigenicity assay and in vitro colony formation, three-dimensional Matrigel culture, cell migration and invasion chamber tests. Notably, overexpression of DUSP6 impairs EMT-associated properties. Furthermore, tissue microarray analysis reveals a clinical association of DUSP6 expression with better patient survival. Taken together, our study provides a novel insight into understanding the functional impact of DUSP6 in tumorigenesis and metastasis of ESCC and NPC.
Original languageEnglish
Pages (from-to)83-95
Number of pages13
JournalInternational Journal of Cancer
Volume130
Issue number1
DOIs
Publication statusPublished - 11 Jan 2012

Keywords

  • dual-specificity phosphatase 6 (DUSP6)
  • tumor suppression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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