Neuropilin-1 upholds dedifferentiation and propagation phenotypes of renal cell carcinoma cells by activating Akt and sonic hedgehog axes. Cancer Res 2008 Nov 01;68(21):8667-72
Date
11/01/2008Pubmed ID
18974107Pubmed Central ID
PMC3964774DOI
10.1158/0008-5472.CAN-08-2614Scopus ID
2-s2.0-55349113212 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
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 DeltaNp63alpha overexpression. Our study reveals that NRP-1 helps maintain an undifferentiated phenotype in cancer cells.
Author List
Cao Y, Wang L, Nandy D, Zhang Y, Basu A, Radisky D, Mukhopadhyay DMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Cell Differentiation
Cell Line, Tumor
DNA Primers
Female
Hedgehog Proteins
Humans
Kidney Neoplasms
Mice
Mice, Nude
Neuropilin-1
Phenotype
Proto-Oncogene Proteins c-akt
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
