Abstract
Background: Upregulation of Heath Shock Protein 70 (HSP70) chaperones supports cancer cell survival. Their high homology causes a challenge to differentiate them in experimental or prevention and treatment strategies. The objective of this investigation was to determine similarities and differences of Hsp70, hsc70, Grp78 and Mortalin members of the HSP70 family encoded by HSPA1, HSPA8, HSPA5 and HSPA9 genes, respectively. Methods: Literature reviews were conducted using HSPA1, HSPA5, HSPA8 and HSPA9 gene or protein names or synonyms combined with biological or cancer-relevant terms. Ingenuity Pathway Analysis was used to identify and compare profiles of proteins that directly bind individual chaperones and their associated pathways. TCGA data was probed to identify associations of hsc70 with cancer patient survival. ClinicalTrials.gov was used to identify HSP70 family studies. Results: The chaperones have similar protein folding functions. Their different cellular effects are determined by co-chaperones and client proteins combined with their intra- and extra-cellular localizations. Their upregulation is associated with worse patient prognosis in multiple cancers and can stimulate tumor immune responses or drug resistance. Their inhibition selectively kills cancer over healthy cells. Conclusions: Differences in Hsp70, hsc70, Grp78 and mortalin provide opportunities to calibrate HSP70 inhibitors for individual cancers and combination therapies.
Highlights
Literature ReviewEach of of the the authors authors independently independently performed performed literature literature searches searches in in online online databases databases
Introduction published maps and institutional affilHeat shock proteins (HSPs) play critical roles in cancer development, progression and drug resistance by assuring proper folding or degradation of unfolded or misfolded proteins [1,2]
The Hsp70, hsc70, Grp78 and mortalin Heath Shock Protein 70 (HSP70) family members have overlapping and unique activities that are likely needed to fine-tune cell survival responses and maintenance of homeostasis
Summary
Each of of the the authors authors independently independently performed performed literature literature searches searches in in online online databases databases Hsc, Grp and mortalin (PubMed and Ovid MEDLINE) for articles related to Hsp, hsc, Grp and mortalin between and. The search terms used were the HSPA1A, HSPA5, HSPA8 between 1965 and 2021. The search terms used were the HSPA1A, HSPA5, HSPA8 and and HSPA9. 2021 were were first first reviewed reviewed to to establish establish themes themes and and earlier earlier articles articles relevant relevant to to the the themes themes were were included included to to assure assure thoroughness thoroughness of of the the review. For specific findings that had numerous publications, either the original or the most. For specific findings had numerous most recent recent publications publications were were cited depending on the context of the sentence
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