Selective abrogation of the proinvasive activity of the trefoil peptides pS2 and spasmolytic polypeptide by disruption of the EGF receptor signaling pathways in kidney and colonic cancer cells

Sylvie Rodrigues, Samir Attoub, Quang Dé Nguyen, Erik Bruyneel, Christelle M. Rodrigue, Bruce R. Westley, Felicity E.B. May, Lars Thim, Marc Mareel, Shahin Emami, Christian Gespach

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Trefoil peptides (TFFs) are now considered as scatter factors, proinvasive and angiogenic agents acting through cyclooxygenase-2 (COX-2)- and thromboxane A2 receptor (TXA2-R)-dependent signaling pathways. As expression and activation levels of the epidermal growth factor receptor (EGFR) predict the metastatic potential of human colorectal cancers, the purpose of this study was to establish whether the EGF receptor tyrosine kinase (EGFR-TK) contributes to cellular invasion induced by TFFs in kidney and colonic cancer cells. Both the dominant negative form of the EGFR (HER-CD533) and the EGFR-TK inhibitor ZD1839 (Iressa) abrogated cellular invasion induced by pS2, spasmolytic polypeptide (SP) and the src oncogene, but not by ITF and the TXA2-R. Similarly, EGFR-TK inhibition by ZD1839 reversed the invasive phenotype promoted by the constitutively activated form of the EGFR (EGFRvIII) and the EGFR agonists transforming growth factor alpha (TGFα), amphiregulin and EGF. We also provide evidence that TFFs, EGFRvIII, and TGFα trigger common proinvasive pathways using the PI3′-kinase and Rho/Rho- kinase cascades. These findings identify the EGFR-TK as a key signaling element for pS2- and SP-mediated cellular invasion. It is concluded that although pS2, SP and ITF belong to the same family of inflammation- and cancer-associated regulatory peptides, they do not control identical signaling networks.

Original languageEnglish
Pages (from-to)4488-4497
Number of pages10
JournalOncogene
Volume22
Issue number29
DOIs
Publication statusPublished - Jul 17 2003
Externally publishedYes

Keywords

  • Bile acids
  • EGFRvIII
  • HER-CD533
  • Iressa
  • Src
  • TXA2-R

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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