Heat Shock Proteins Promote Cancer: It's a Protection Racket

Heat shock proteins (HSP) are expressed at high levels in cancer and form a fostering environment that is essential for tumor development. Here, we review the recent data in this area, concentrating mainly on Hsp27, Hsp70, and Hsp90. The overriding role of HSPs in cancer is to stabilize the active functions of overexpressed and mutated cancer genes. Thus, elevated HSPs are required for many of the traits that underlie the morbidity of cancer, including increased growth, survival, and formation of secondary cancers. In addition, HSPs participate in the evolution of cancer treatment resistance. HSPs are also released from cancer cells and influence malignant properties by receptor-mediated signaling. Current data strongly support efforts to target HSPs in cancer treatment. Molecular chaperones, such as Hsp27, Hsp70, and Hsp90, have elevated expression in a range of cancers, which indicates a poor prognosis in most cases. HSP expression is essential to many of the distinctive traits of malignant cells, including uncontrolled growth, reduced tumor suppression, enhanced cell survival, and angiogenic and metastatic properties. Recent studies show that HSPs support cancer stem cell identity, including the capacity for cell renewal, invasion, and metastasis. Increased levels of Hsp90 aid the rapid evolution of new treatment-resistant phenotypes by permitting new traits to arise within tumors. HSPs can interact distinctly with different driver oncogenes, which drives the progression of individual cancers. Extracellular HSPs are of growing importance in the etiology of cancer and may mediate powerful effects on tumor immunity and metastasis.