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Biomarker: HSP27 (pS78)

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HSP27 (pS78)

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Status:

Experienced Running

Biological or Clinical Significance:

Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis-inducing agents such as tumor necrosis factor-α (TNFα), staurosporin, and doxorubicin. This role leads to its involvement in many pathological processes, such as oncogenesis, neurodegeneration, and senescence.

Elevated Hsp70 levels in tumor cells may increase malignancy and resistance to therapy by complexing, and hence, stabilizing, oncofetal proteins and products and transporting them into intracellular sites, thereby promoting tumor cell proliferation. As a result, tumor vaccine strategies for Hsp70s have been highly successful in animal models and progressed to clinical trials. Alternatively, overexpression of Hsp70 can mitigate the effects of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s corea, and spinocerebellar ataxias, and aging and cell senescence, as observed in centenarians subjected to heat shock challenge. Protein kinase C-mediated HSPB1 phosphorylation protects against ferroptosis, an iron-dependent form of non-apoptotic cell death, by reducing iron-mediated production of lipid reactive oxygen species. These novel data support the development of Hsp-targeting strategies and, specifically, anti-HSP27 agents for the treatment of ferroptosis-mediated cancer.

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