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These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration.
The PHIP gene resides on 6q14.1, and although 6q loss has been observed in melanoma, the PHIP locus was preserved in melanoma cell lines and patient samples, and its overexpression was an independent adverse predictor of survival in melanoma patients.
Systemic, plasmid-based shRNA targeting of Phip inhibited the metastatic progression of melanoma, whereas stable suppression of Phip in melanoma cell lines suppressed metastatic potential and prolonged the survival of tumor-bearing mice.
Together these results suggest that PHIP1 regulates postnatal growth in an IGF-1 (zeige IGF1 Proteine)/AKT (zeige AKT1 Proteine) pathway-independent manner.
Identification of a WD40 (zeige DCAF12L2 Proteine) repeat-containing isoform of Phip as a novel regulator of beta-cell growth and survival.
PHIP binds the pleckstrin homology (PH) domain of insulin receptor substrate-1 (IRS1\; MIM 147545), modulates insulin signaling, and plays a role in pancreatic beta cell growth and survival (Farhang-Fallah et al., 2000
DDB1 and CUL4 associated factor 14
, IRS-1 PH domain-binding protein
, PH-interacting protein
, WD repeat-containing protein 11
, WD repeat domain 11
, neuronal differentiation related protein
, neuronal differentiation-related protein
, pleckstrin homology domain interacting protein
, LOW QUALITY PROTEIN: PH-interacting protein