Neuropilin-1 upholds dedifferentiation and propagation phenotypes of renal cell carcinoma cells by activating Akt and sonic hedgehog axes

Ying Cao, Ling Wang, Debashis Nandy, Ying Zhang, Ananda Basu, Derek Radisky, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Expression of neuropilin-1 (NRP-1) has been shown in many cancer cells, but its molecular effect on tumorigenesis is largely unknown. In this report, we show that in aggressive types of renal cell carcinoma (RCC), NRP-1 is expressed at a high level. We show that after knockdown of NRP-1 by short hairpin RNA, RCC cells express significantly lower levels of MDM-2 and p63 proteins but higher levels of p53, and exhibit reduced migration and invasion. When implanted in mice, RCC cells with a reduced NRP-1 level have a statistically significant smaller tumor-forming ability than control cells. Also, NRP-1 knockdown RCC cells exhibit a more differentiated phenotype, as evidenced by the expression of epithelial-specific and kidney-specific cadherins, and the inhibition of sonic hedgehog expression participated in this effect. Inhibition of sonic hedgehog expression can be reversed by ΔNp63α overexpression. Our study reveals that NRP-1 helps maintain an undifferentiated phenotype in cancer cells.

Original languageEnglish (US)
Pages (from-to)8667-8672
Number of pages6
JournalCancer research
Volume68
Issue number21
DOIs
StatePublished - Nov 1 2008

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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