Abstract
The cellular response to cancer-induced stress is one of the major aspects regulating cancer development and progression. The Heat Shock Protein B8 (HSPB8) is a small chaperone involved in chaperone-assisted selective autophagy (CASA). CASA promotes the selective degradation of proteins to counteract cell stress such as tumor-induced stress. HSPB8 is also involved in (i) the cell division machinery regulating chromosome segregation and cell cycle arrest in the G0/G1 phase and (ii) inflammation regulating dendritic cell maturation and cytokine production. HSPB8 expression and role are tumor-specific, showing a dual and opposite role. Interestingly, HSPB8 may be involved in the acquisition of chemoresistance to drugs. Despite the fact the mechanisms of HSPB8-mediated CASA activation in tumors need further studies, HSPB8 could represent an important factor in cancer induction and progression and it may be a potential target for anticancer treatment in specific types of cancer. In this review, we will discuss the molecular mechanism underlying HSPB8 roles in normal and cancer conditions. The basic mechanisms involved in anti- and pro-tumoral activities of HSPB8 are deeply discussed together with the pathways that modulate HSPB8 expression, in order to outline molecules with a beneficial effect for cancer cell growth, migration, and death.
Highlights
Human cells have different fine-tuned systems that act as defense mechanisms against a large number of different environmental stresses
In Alzheimer disease (AD), in which the role of different HSPBs was analyzed, it was demonstrated that Heat Shock Protein B8 (HSPB8), HSPB6, and HSPB2 co-localize with cerebral amyloid angiopathy (CAA) in AD brains; notably, in human leptomeningeal smooth muscle cells and human brain astrocytes, HSPB8 increases the secretion of the inflammatory factors interleukin-8 (IL-8), soluble ICAM-1, and monocyte chemoattractant protein 1, suggesting that HSPB8, possibly working in conjunction with other HSPBs, can act as a mediator of the inflammatory reactions associated with CAA [82]
All data reported in this review suggest that HSPB8 is deeply involved in the modulation of the appearance and the progression of many types of cancer in humans
Summary
Human cells have different fine-tuned systems that act as defense mechanisms against a large number of different environmental stresses. Chaperones were originally grouped based on their apparent molecular mass, while they are classified mainly by their functions in the folding processes (HSP110s, HSP90s, HSP70s, HSP60s, HSP40s, and small heat shock proteins (sHSPs)), but there are similarities between the two nomenclatures; based on the HUGO Gene Nomenclature Committee, the new classification recently adopted is as follows: HSPB (sHSP), DNAJ (HSP40), HSPD (HSP60), HSPA (HSP70), HSPC (HSP90), and HSPH (HSP110) [3], and reflects both the functions and the sizes of the members of each subfamily. The human genome encodes 10 HSPBs named HSPB1 through HSPB10, with an apparent molecular mass of 12–43 kDa [8] Despite their name, the expression of HSPBs can be dependently or independently regulated by heat shock transcription factors (HSFs). (BAG3), which is thought to be the obligate partner of HSPB8 [18,19]
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