Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors

Weigang Wang, Sumanta Goswami, Kyle Lapidus, Amber L. Wells, Jeffrey B. Wyckoff, Erik Sahai, Robert H. Singer, Jeffrey E. Segall, John S. Condeelis

Research output: Contribution to journalArticle

338 Scopus citations

Abstract

We subjected cells collected using an in vivo invasion assay to cDNA microarray analysis to identify the gene expression profile of invasive carcinoma cells in primary mammary tumors. Expression of genes involved in cell division, survival, and cell motility were most dramatically changed in invasive cells indicating a population that is neither dividing nor apoptotic but intensely motile. In particular, the genes coding for the minimum motility machine that regulates β-actin polymerization at the leading edge and, therefore, the motility and chemotaxis of carcinoma cells, were dramatically up-regulated. However, ZBP1, which restricts the localization of β-actin, the substrate for the minimum motility machine, was down-regulated. This pattern of expression implicated ZBP1 as a suppressor of invasion. Reexpression of ZBP1 in metastatic cells with otherwise low levels of ZBP1 reestablished normal patterns of β-actin mRNA targeting and suppressed chemotaxis and invasion in primary tumors. ZBP1 reexpression also inhibited metastasis from tumors. These experiments support the involvement in metastasis of the pathways identified in invasive cells, which are regulated by ZBP1.

Original languageEnglish (US)
Pages (from-to)8585-8594
Number of pages10
JournalCancer research
Volume64
Issue number23
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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