CTGF enhances the motility of breast cancer cells via an integrin-αvβ3-ERK1/2-dependent S100A4-upregulated pathway

Pai Sheng Chen, Ming Yang Wang, Shin Ni Wu, Jen Liang Su, Chih Chen Hong, Shuang En Chuang, Min Wei Chen, Kuo Tai Hua, Yu Ling Wu, Shih Ting Cha, Munisamy Suresh Babu, Chiung Nien Chen, Po Huang Lee, King Jen Chang, Min Liang Kuo

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

Connective tissue growth factor (CTGF) expression is elevated in advanced stages of breast cancer, but the regulatory role of CTGF in invasive breast cancer cell phenotypes is unclear. Presently, overexpression of CTGF in MCF-7 cells (MCF-7/CTGF cells) enhanced cellular migratory ability and spindle-like morphological alterations, as evidenced by actin polymerization and focal-adhesion-complex aggregation. Reducing the CTGF level in NDA-MB-231 (MDA231) cells by antisense CTGF cDNA (MDA231/AS cells) impaired cellular migration and promoted a change to an epithelial-like morphology. A neutralizing antibody against integrin αvβ3 significantly attenuated CTGF-mediated ERK1/2 activation and cellular migration, indicating that the integrin-αvβ3-ERK1/2 signaling pathway is crucial in mediating CTGF function. Moreover, the cDNA microarray analysis revealed CTGF-mediated regulation of the prometastatic gene S100A4. Transfection of MCF-7/CTGF cells with AS-S100A4 reversed the CTGF-induced cellular migratory ability, whereas overexpression of S100A4 in MDA231/AS cells restored their high migratory ability. Genetic and pharmacological manipulations suggested that the CTGF-mediated S100A4 upregulation was dependent on ERK1/2 activation, with expression levels of CTGF and S100A4 being closely correlated with human breast tumors. We conclude that CTGF plays a crucial role in migratory/invasive processes in human breast cancer by a mechanism involving activation of the integrin-αvβ3-ERK1/2-S100A4 pathway.

Original languageEnglish
Pages (from-to)2053-2065
Number of pages13
JournalJournal of Cell Science
Volume120
Issue number12
DOIs
Publication statusPublished - 2007 Jun 15

All Science Journal Classification (ASJC) codes

  • Cell Biology

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