Regulatory Roles for Hsp70 in Cancer Incidence and Tumor Progression
Pp. 1-22 (22)
Taka Eguchi, Benjamin J. Lang, Ayesha Murshid, Thomas Prince, Jianlin Gong and Stuart K Calderwood
The HSP70 family of molecular chaperones plays a significant role in
cancer. Notably, the inducible protein Hsp72 becomes expressed in many cancers,
often to high levels and underlies escape of tumor cells from senescence and increased
tumor initiation and metastasis. Examination of database suggests that mutation within
the ORFs of HSP70 genes in cancer is relatively rare suggesting a requirement for
intact function. At the molecular level, Hsp72 is thought to chaperone key proteins in
tumorigenesis and permit their accumulation in the malignant cell. In addition, an
important role for Hsp72 in RNA metabolism is emerging, indicating mechanisms
potentially involving the RNA binding protein HuR. The existence of multiple HSP70
pseudogenes may also be important for future studies of long non-coding RNA
(lncRNA) regulation through this family of chaperones. As the significance of this
family of chaperones in cancer emerges, small molecule inhibitors have been
developed as future potential cancer pharmaceuticals. We discuss the targeting of
individual HSP70 families at key functional domains in the proteins.
Heat shock protein seventy, Structure, Function, Cancer, Growth,
Metastasis, Chemical inhibitor, Substrate, Domain, ATPase, Drug.
Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA02115, USA.