IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis.
IMP1 is frequently overexpressed in cancer and is strongly correlated with a poor prognosis and reduced survival in melanoma, ovarian, breast, colon, and lung cancer.
Signal peptide peptidase-mediated nuclear localization of heme oxygenase-1 promotes cancer cell proliferation and invasion independent of its enzymatic activity.
Interestingly, stromal deletion of Imp1 (Dermo1Cre;Imp1(LoxP/LoxP), or Imp1(ΔMes)) in the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colitis-associated cancer resulted in increased tumor numbers of larger size and more advanced histologic grade than controls.
Cellular invasive activity of IMP-1 on mammalian cells was examined using Matrigel assays. mRNAs associated with IMP-1 in cancer cells were also isolated by RNA immunoprecipitation followed by cDNA microarray analysis.
These data 1) suggest a normal role for CRD-BP/IMP1 in pluripotent stem cells with high renewal capacity, like the CB CD34(+) cells, 2) indicate that altered methylation may directly or indirectly affect its expression in adult cells, 3) imply that its de novo activation in cancer cells may affect the expression of c-Myc and insulin-like growth factor II, and 4) indicate that the inhibition of CRD-BP/IMP1 expression might affect cancer cell proliferation.