SLIT2 attenuation during lung cancer progression deregulates β-catenin and E-cadherin and associates with poor prognosis

Ruo Chia Tseng, Shih Hua Lee, Han Shui Hsu, Ben Han Chen, Wan Ching Tsai, Ching Tzao, Yi-Ching Wang

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Chromosome 4p15.3 is frequently deleted in late-stage lung cancer. We investigated the significance of the SLIT2 gene located in this region to lung cancer progression. SLIT2 encodes an extracellular glycoprotein that can suppress breast cancer by regulating β-catenin. In this study, we examined alterations in the structure or expression of SLIT2, its receptor ROBO1, and β-catenin, along with the AKT/glycogen synthase kinase 3β (GSK3β)/β-transducin repeat-containing protein (βTrCP) pathway in lung cancer cell lines and patients. Low SLIT2 expression correlated with an upward trend of pathological stage and poorer survival in lung cancer patients. Importantly, SLIT2, βTrCP, and β-catenin expression levels predicted postoperative recurrence of lung cancer in patients. Stimulating SLIT2 expression by various methods increased the level of E-cadherin caused by attenuation of its transcriptional repressor SNAI1. Conversely, knocking down SLIT2 expression increased cell migration and reduced cell adhesion through coordinated deregulation of β-catenin and E-cadherin/SNAI1 in the AKT/GSK3β/βTrCP pathway. Our findings indicate that SLIT2 suppresses lung cancer progression, defining it as a novel "theranostic" factor with potential as a therapeutic target and prognostic predictor in lung cancer.

Original languageEnglish
Pages (from-to)543-551
Number of pages9
JournalCancer Research
Volume70
Issue number2
DOIs
Publication statusPublished - 2010 Jan 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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