The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics

Abstract

Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e.g., HSP10 and HSP27), HSP40, HSP60, HSP70, HSP90, and the category of large HSPs that include HSP100 and ClpB proteins. The overexpression of HSPs is induced to counteract cell stress at elevated levels in a variety of solid tumors, including anticancer chemotherapy, and is closely related to a worse prognosis and therapeutic resistance to cancer cells. HSPs are also involved in anti-apoptotic properties and are associated with processes of cancer progression and development, such as metastasis, invasion, and cell proliferation. This review outlines the previously mentioned HSPs and their significant involvement in diverse mechanisms of tumor advancement and metastasis, as well as their contribution to identifying potential targets for therapeutic interventions.

Impact of Polyethylene Terephthalate Microplastics on Drosophila melanogaster Biological Profiles and Heat Shock Protein Levels

“…Our study sheds light on the toxicity of microplastics through the involvement of different hsp genes in defense mechanisms against PET microplastics. Ultimately, our findings suggest that the overexpression of specific stress genes could indicate impending health threats from microplastics, serving as early indicators of toxicity [59]. Numerous studies have highlighted metabolic disturbances, neurotoxicity, and increased cancer risk in humans following exposure to microplastics [61].…”

“…Elevated levels of heat shock proteins (HSPs) are a defensive reaction to stress [57], and moreover, hsp26, hsp90, and hsp70 are stress-inducible HSPs that have been the subject of extensive research [58]. Previous studies have demonstrated that malignancy is characterized by a substantial increase in the expression and activity of these chaperones, which are also susceptible to various stimuli that induce cell death [59].…”

Mixtures of Three Mortaparibs with Enhanced Anticancer, Anti-Migration, and Antistress Activities: Molecular Characterization in p53-Null Cancer Cells

“…Molecular chaperones that regulate stress response as a first line of defense by attenuating ROS and facilitating the correct conformation and intracellular localization of proteins have been considered therapeutic targets for age-related metabolic diseases and cancer [ 7 , 8 ]. The latter is commonly associated with the overexpression of stress chaperones (including HSP40, HSP60, HSP70, and HSP90) that play a substantial role in hyper-proliferation and anti-apoptotic characteristics of tumors and hence are also used as tumor biomarkers [ 9 ]. Besides their overexpression, the subcellular localization of these molecular chaperones is modulated during physiologically stressful conditions and cancer.…”