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Membrane bound prenylated C17orf37 is a critical regulator of cancer cell migration and invasion
Author(s) -
Dasgupta Subhamoy,
Gryczynski Zygmunt,
Vishwanatha Jamboor K
Publication year - 2009
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.23.1_supplement.878.8
Subject(s) - microbiology and biotechnology , cancer cell , lncap , annexin , cell migration , gene knockdown , prenylation , protein kinase b , biology , pi3k/akt/mtor pathway , annexin a2 , chemistry , cell , signal transduction , cell culture , cancer , enzyme , flow cytometry , biochemistry , genetics
C17orf37 is located in the hot spot locus of human chromosomal region 17q12‐21 next to ErbB2. Previously we have shown that C17orf37 expression is significantly higher in prostate cancer cells and tissue specimens compared to normal prostate cells. By gene knock down studies, we demonstrated that C17orf37 regulates prostate cancer cell migration and invasion by modulating key proteins involved in these processes, such as MMP‐9, uPA and VEGF. The migration‐defect phenotype in C17orf37 depleted prostate cancer cells were restored on C17orf37 overexpression, with concomitant increased expression of MMP‐9, uPA and VEGF proteins. Knockdown of C17orf37 abolished p‐Akt and reduced DNA binding activity of NF‐κB. Cellular localization studies using confocal and TIRF microscopy demonstrated predominant expression of C17orf37 protein in the membrane. C17orf37 protein has a C‐terminal prenylation motif 'CVIL' and using inhibitors of prenyl transferase enzymes we demonstrate that C17orf37 is preferentially geranylgeranylated by GGTase‐1 enzyme and this inhibition results in reduced membrane bound C17orf37. We identified annexin A2 as a novel interactor of C17orf37 and by FLIM based FRET assay we found that these two molecules physically interact at the membrane region. Our studies show C17orf37‐annexin A2 interaction is critical for tumor cell migration and invasion, by regulating downstream signaling molecules. ( Supported grants from the National Institutes of Health CA109593 and MD 001633)