The Chaperone Hsp90, a Key Player in Salivary Gland Tumorigenesis

Abstract

The chaperone system (CS) is emerging as a key multistage participant in carcinogenesis. The CS chief components are the molecular chaperones (some of which are named heat shock proteins or Hsp), which are typically cytoprotective but if abnormal in structure, location, or quantity, can become etiopathogenic and cause diseases, known as chaperonopathies, including some cancers. For example, abnormal Hsp90 expression is associated with tumorigenesis and poor prognosis. Hsp90 is positioned at the center of several key oncogenic pathways by stabilizing and activating oncogenic kinases responsible for driving cell proliferation and survival. Consequently, inhibition of Hsp90 is being investigated as a possible anti-cancer strategy and some results are encouraging. However, the 5-year survival rate for patients suffering from salivary gland carcinomas is still unsatisfactory. Because of the rarity of these malignancies, they may have been overlooked and understudied and, thus, novel therapies (e.g., inhibition of CS components like Hsp90 and others) are urgently needed. In this review, we also summarize the histopathological quantitative patterns and the intra- and extra-cellular location characteristics of Hsp90 in tumors of salivary glands, pointing to their potential for differential diagnosis, prognostication, and patient monitoring.