Huntingtin Interacting Protein 1 (HIP1) is a clathrin, actin and inositol lipid binding protein that has been shown to modulate endocytic pathways. HIP1 was originally associated with cancer by the discovery of the oncogenic HIP1/PDGF(3R fusionMoreHuntingtin Interacting Protein 1 (HIP1) is a clathrin, actin and inositol lipid binding protein that has been shown to modulate endocytic pathways.
HIP1 was originally associated with cancer by the discovery of the oncogenic HIP1/PDGF(3R fusion protein that resulted from a t(5-7) chromosomal translocation in a patient with leukemia. HIP1 has since been implicated in a variety of additional cancers, as we show here that it is frequently over expressed in breast cancer, glial brain tumors, and lymphoma. We have found previously that HIP1 over-expression predicts a bad outcome in human prostate cancer, transforms fibroblasts in culture and is necessary for prostate cancer progression in mice.
Genetic deletion of HIP1 together with its only known mammalian relative, HIP1r, has profound physiologic effects on the mouse that include spinal defects, weight loss and premature death between one and eight months of age. Remarkably, we have found that transgenic expression of the human HIP1 protein in the double HIP1/HIP1r mutant mice rescues all of these phenotypes. These genetic data confirm that HIP1 is necessary for the maintenance of multiple normal adult cell types and that the human HIP1 protein is functionally similar to the mouse HIP1 and HIP1r proteins.
Finally, we show here that sera from individuals with prostate cancer, glioblastoma, oligodendroglioma, and lymphoma specifically contain anti-HIP1 antibodies. These discoveries provide strong support for the idea that HIP1 expression is required for the proliferation or survival of certain types of both normal and cancerous cells. Better understanding of when and how HIP1 is altered in newly diagnosed or recurrent cancers will lead to the development of more in depth investigations into the use of screens for HIP1 abnormalities in both the clinical and basic areas of cancer research.