Functional characterization of Trip10 in cancer cell growth and survival

We applied methylation-specific polymerase chain reaction and bisulfite sequencing to determine the DNA methylation of Trip10 in various cancer cell lines and tumor specimens. We also overexpressed Trip10 to observe its effect on colony formation and in vivo tumorigenesis.We found that Trip10 is hypermethylated in brain tumor and breast cancer, but hypomethylated in liver cancer. Overexpressed Trip10 was associated with endogenous Cdc42 and huntingtin in IMR-32 brain tumor cells and CP70 ovarian cancer cells. However, overexpression of Trip10 promoted colony formation in IMR-32 cells and tumorigenesis in mice inoculated with IMR-32 cells, whereas overexpressed Trip10 substantially suppressed colony formation in CP70 cells and tumorigenesis in mice inoculated with CP70 cells.Trip10 regulates cancer cell growth and death in a cancer type-specific manner. Differential DNA methylation of Trip10 can either promote cell survival or cell death in a cell type-dependent manner.Trip10 is a scaffold protein with F-BAR, ERM, and SH3 domains. Because these domains interact with diverse signaling partners, Trip10 is involved in various cellular processes including insulin-stimulated glucose uptake, endocytosis, cytoskeleton arrangement, membrane invagination, proliferation, survival, and migration, in a tissue-specific and cell lineage-specific manner. In adipocytes, Trip10 increases glucose uptake by interacting with TC-10 to regulate insulin-stimulated glucose transporter 4 (Glut4) translocation to the plasma membrane [1,2]. However, in muscle cells, Trip10 inhibits glucose uptake by increasing Glut4 endocytosis [3,4]. In natural killer cells, Trip10 regulates actin cytoskeleton dynamics by interacting with WASP protein [5,6], and regulates cytotoxicity by facilitating localization of microtubule organizing centers to immunological synapses [7]. Trip10 is also a regulator or modulator of cell survival after DNA damage [8] and in the human brain affected by Huntington's disease