![]() Consequently, we have implemented projects taking into account the complexity of the CS and its functional connections in the body, even if the research must proceed one step at a time, because it is unfeasible to study all the components of the CS simultaneously. Therefore, developing treatments based on those studies circumscribed to one or a few chaperones and ignoring the other components of the CS and its main interactors, i.e., UPS, CMA, and IS, may be disappointing, as already demonstrated by a number of investigators. The interpretation of results is difficult, if not impossible, because of incomplete information. It follows that the study of one or a few molecular chaperones and the estimation of their value as biomarkers in BC do not cover the entire range of their capabilities and the mechanisms in which they participate. For instance, the CS interacts with the immune system (IS) in performing some of its non-canonical functions in cancer and inflammatory and autoimmune conditions. The CS also displays non-canonical functions unrelated to protein quality control but pertaining to other mechanisms. Furthermore, in performing its canonical functions pertaining to protein homeostasis, the CS collaborates with the Ubiquitin–Proteasome System (UPS) and the chaperone-mediated autophagy (CMA) machinery. The chaperones typically form teams that interact to build functional networks for the maintenance of protein homeostasis in the entire body, as well as in tumor tissue. The latter is composed of molecular chaperones, chaperone co-factors, co-chaperones, and chaperone interactors and receptors. It has become increasingly clear that chaperones do not act alone, but rather in conjunction with the other components of the CS. We have undertaken research on the role of the CS in various tumors starting from histological studies to quantify and map diverse chaperones in the tumor tissue and continuing with the detection of chaperones in EVs released by the tumors. Despite the many reports on the levels of molecular chaperones, i.e., the chief components of the CS, in tumor tissue and a variety of samples from patients, and despite experiments to determine their role in the tumor’s biology, there are still key mechanisms in which chaperones and the other components of the CS most likely participate that have not been elucidated. For example, the role of the chaperone system (CS) in tumor initiation, progression, and resistance to treatment, as well as in anti-tumor mechanisms, is still poorly understood. However, there are still various unresolved issues that need clarification for developing accurate and fast diagnostic tests, reliable disease-monitoring strategies, and efficacious treatments. Laboratory and clinical research on breast cancer (BC) has been intensive for many years because of the high frequency and malignancy of the diverse forms of this tumor. ![]() An integrated view of the CS, including its functional partners and considering its highly dynamic nature with EVs transporting CS components to reach all the cell compartments in which they are needed, opens as yet unexplored pathways leading to carcinogenesis that are amenable to interference by anti-cancer treatments centered on CS components, such as the molecular chaperones. The data surveyed from many laboratories reveal that, to enhance the understanding of the role of the CS in BS pathogenesis, one must consider the CS as a physiological system, encompassing diverse members throughout the body and interacting with the ubiquitin–proteasome system, the chaperone-mediated autophagy machinery, and the immune system (IS). ![]() Extracellular vesicles (EVs) in BC diagnosis and management are also briefly discussed, considering their potential as easily accessible carriers of biomarkers and as shippers of anti-cancer agents amenable to manipulation and controlled delivery. The chaperones can also be employed in immunotherapy against BC as adjuvants, together with BC antigens. These chaperones can be targets of negative chaperonotherapy, namely the elimination/blocking/inhibition of the chaperone(s) functioning in favor of BC, using, for instance, Hsp inhibitors. The chief components of the CS are the molecular chaperones, and here we discuss four of them, Hsp27, Hsp60, Hsp70, and Hsp90, focusing on their pro-carcinogenic roles in BC and potential for developing anti-BC therapies. For example, the participation of the chaperone system (CS) in carcinogenesis and anti-cancer responses is poorly understood, although it can be predicted to be a crucial factor in these mechanisms. Breast cancer (BC) is a major public health problem, with key pieces of information needed for developing preventive and curative measures still missing. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |