Tumor necrosis factor receptor-associated protein 1(TRAP1) regulates genes involved in cell cycle and metastases.

Abstract

Tumor necrosis factor (TNF) receptor-associated protein 1(TRAP1/HSP75) is a heat shock protein, highly homologous to HSP90, which acts as a molecular chaperone to retinoblastoma protein (Rb) during cellular stress although the current literature suggests that this protein could have additional functions. The aim of this study was to identify the pathways regulated by TRAP1. TRAP1 was silenced by siRNA in A549 cells and re-expressed by stable transfection in MDA231 cells. After growing the cells for 16 h under normoxic or hypoxic conditions, oligonucleotide microarrays were employed to detect differentially expressed genes.

In TRAP1 positive cells there are high levels of cell proliferation promoting genes coding for G protein coupled receptors, cell adhesion genes and genes associated with Rho-kinase pathways. In TRAP1 negative cells there are higher levels of genes involved in cell motility and metastatic spread. Pathway map analysis shows that TRAP1 controls cell cycle activity through the tumor necrosis factor pathways. Our data suggest that in many tumors TRAP1 could activate proliferation whilst inhibiting metastatic spread.