Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers

Jianbo Wang, Ryan Day, Yiyu Dong, Steven J. Weintraub, Loren Michel

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

The cell surface protein Trop-2 is highly expressed in a wide variety of epithelial cancers. In contrast, there is little or no expression of Trop-2 in adult somatic tissue. Because it is a cell surface protein that is selectively expressed in tumor cells, Trop-2 is a potential therapeutic target. However, whether Trop-2 is actively involved in tumorigenesis and whether its targeting for treatment would be effective have not been examined. Here, we show that Trop-2 expression is necessary for tumorigenesis and invasiveness of colon cancer cells, as both are inhibited when Trop-2 expression is suppressed by RNA interference. Conversely, ectopic expression of Trop-2 in colon cancer cells enhances their capacity for anchorage-independent growth and ectopic expression of Trop-2 in NIH3T3 cells is sufficient to promote both anchorage-independent growth and tumorigenesis. Importantly, we show that an antibody against the extracellular domain of Trop-2 reduces tumor cell invasiveness. Therefore, we have identified Trop-2 as an oncogene that has potential as a therapeutic target. Given the restricted expression of Trop-2 in normal tissue, anti-Trop-2 therapeutics would be predicted to have limited toxicity.

Original languageEnglish
Pages (from-to)280-285
Number of pages6
JournalMolecular Cancer Therapeutics
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2008

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