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C17orf37 regulates prostate cancer cell migration and invasion by NF‐kB mediated downstream target genes
Author(s) -
Dasgupta Subhamoy,
Vishwanatha Jamboor K
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.646.8
Subject(s) - lncap , prostate cancer , gene knockdown , protein kinase b , cancer cell , pi3k/akt/mtor pathway , biology , microbiology and biotechnology , annexin a2 , cancer research , annexin , signal transduction , gene , cancer , flow cytometry , genetics
C17orf37/MGC14832 is located in the hot spot locus of human chromosomal region 17q12‐21 next to ErbB2. Earlier we have characterized C17orf37 protein, and have shown the protein expression significantly higher in prostate cancer cells and tissue specimens compared to normal prostate cells. By gene knock down studies, we have found C17orf37 regulates prostate cancer cell migration and invasion by modulating certain key proteins involved in the process like MMP‐9, uPA and VEGF. Here we hypothesize that C17orf37 acts as a membrane bound signaling molecule and facilitates migration and invasion of prostate cancer cells by NF‐kB mediated downstream target genes. Our results show that knockdown of C17orf37 in DU‐145 prostate cancer cells by increasing concentration of gene specific siRNA significantly reduced the DNA binding activity of NF‐kB in a dose dependent manner. Furthermore, C17orf37 knockdown also decreased the activated phosphorylated Akt to inactive form suggesting C17orf37 must be located upstream of Akt. Imaging DU‐145 and LNCaP prostate cancer cells by total internal reflection fluorescence microscopy we have observed C17orf37 on the membrane of these cells and this observation is supported by the fact that C17orf37 has a potential prenylation motif. By Fluorescence Lifetime Imaging Microscopy based FRET assys we have located the C17orf37 interacts with annexin A2 mostly in the membrane and perinuclear region. Currently we are investigating the functional significance of C17orf37 and annexin A2 interaction and the downstream signaling cascade that regulates migration and invasion in prostate cancer cells. (Supported grants from the National Institutes of Health CA109593 and MD 001633)