HSPA8 and HSPA9: Two prognostic and therapeutic targets in breast, colon, and kidney cancers?

The process of protein folding is important to ensure the efficient functioning of cells. The capacity of a protein to attain the three-dimensional native conformation can impact its structure and function. Errors in this process result in the accumulation of misfolded proteins, which can contribute to the development of various diseases, including cancer. To prevent the pileup of misfolded proteins, a number of control systems have been developed over the course of evolution. In this scenario, a pivotal function has been attributed to molecular chaperones and the ubiquitin-proteasome degradation system. In this paper, we concentrate on molecular chaperones, with a particular focus on a family of heat shock proteins (HSPs), to highlight any potential correlation between their expression and function and the development of cancer. Hence, we have collected data from various public databases regarding the HSP70 protein family. By employing mRNA expression signatures, prognostic value analysis, and differentially expressed gene ontology analysis, we have elucidated the tumor-specific role of two members of the HSP70 family, namely HSPA8 and HSPA9, in kidney renal clear cell carcinoma (KIRC), colon adenocarcinoma (COAD), and breast invasive carcinoma (BRCA). Our research shed light on the controversial and tumor-specific role of HSP70s. More in detail, we have identified HSPA8 and HSPA9 as potential prognostic and therapeutic targets involved in several biological processes leading to tumorigenesis, including nucleic acid maturation, cell signaling, vesicle trafficking, mitochondrial structure and function, and protein maturation.