EN
TRAP1 is an HSP90 chaperone, upregulated in
human cancers and involved in organelles’ homeostasis
and tumor cell metabolism. Indeed, TRAP1 is a key
regulator of adaptive responses used by highly proliferative
tumors to face the metabolic stress induced by increased
demand of protein synthesis and hostile environments.
Besides well-characterized roles in prevention of
mitochondrial permeability transition pore opening and
in regulating mitochondrial respiration, TRAP1 is involved
in novel regulatory mechanisms: i) the attenuation
of global protein synthesis, ii) the co-translational
regulation of protein synthesis and ubiquitination of
specific client proteins, and iii) the protection from
Endoplasmic Reticulum stress. This provides a crucial role
to TRAP1 in maintaining cellular homeostasis through
protein quality control, by avoiding the accumulation of
damaged or misfolded proteins and, likely, facilitating
the synthesis of selective cancer-related proteins. Herein,
we summarize how these regulatory mechanisms are
part of an integrated network, which enables cancer cells
to modulate their metabolism and to face, at the same
time, oxidative and metabolic stress, oxygen and nutrient
deprivation, increased demand of energy production and
macromolecule biosynthesis. The possibility to undertake
a new strategy to disrupt such networks of integrated
control in cancer cells holds great promise for treatment
of human malignancies.