The endoplasmic reticulum (ER) is an important subcellular organelle that is involved in numerous activities required to achieve and maintain functional proteins in addition to its role in the biosynthesis of lipids and as a repository of intracellular Ca2+. The inability of the ER to cope with protein folding beyond its capacity causes disturbances that evoke ER stress. Cells possess molecular mechanisms aimed at clearing unwanted cargo from the ER lumen as an adaptive response, but failing to do so navigates the system towards cell death. This systemic approach is called the unfolded protein response. Aging insults cells through various perturbations in homeostasis that involve curtailing ER function by mitigating the expression of its resident chaperones and enzymes. Here the unfolded protein response (UPR) cannot protect the cell due to the weakening of its protective arm, which exacerbates imbalanced homeostasis. Aging predisposed breast malignancy activates the UPR, but tumor cells maneuver the mechanistic details of the UPR, favoring tumorigenesis and thereby eliciting a treacherous condition. Tumor cells exploit UPR pathways via crosstalk involving various signaling cascades that usher tumor cells to immortality. This review aims to present a collection of data that can delineate the missing links of molecular signatures between aging and breast cancer.
The etiopathologies behind autoimmune thyroid diseases (AITDs) unravel misbehavior of immune components leading to the corruption of immune homeostasis where thyroid autoantigens turn foe to the self. In AITDs lymphocytic infiltration in the thyroid shows up a deranged immune system charging the follicular cells of the thyroid gland (thyrocytes) leading to the condition of either hyperthyroidism or hypothyroidism. The inflammation in AITDs consistently associate with ER function due to which disturbances in the ER protein homeostasis leads to unfolded protein response (UPR) that promotes pathogenesis of autoimmunity. The roles of ER stress in the instantaneous downregulation of MHC class I molecules on thyrocytes and the relevance of IFN γ in the pathogenesis of AITD has been well-documented. Thyroglobulin being the major target of autoantibodies in most of the AITDs is because of its unusual processing in the ER. Autoimmune disorders display a conglomeration of ER stress-induced UPR activated molecules. Several epidemiological data highlight the preponderance of AITDs in women as well as its concurrence with breast cancer. Both being an active glandular system displaying endocrine activity, thyroid as well as breast tissue show various commonalities in the expression pattern of heterogenous molecules that not only participate in the normal functioning but at the same time share the blame during disease establishment. Studies on the development and progression of breast carcinoma display a deranged and uncontrolled immune response, which is meticulously exploited during tumor metastasis. The molecular crosstalks between AITDs and breast tumor microenvironment rely on active participation of immune cells. The induction of ER stress by Tunicamycin advocates to provide a model for cancer therapy by intervening glycosylation. Therefore, this review attempts to showcase the molecules that are involved in feeding up the relationship between breast carcinoma and AITDs.
Cannabinoids, commonly used for medicinal and recreational purposes, consist of various complex hydrophobic molecules obtained from Cannabis sativa L. Acting as an inhibitory molecule; they have been investigated for their antineoplastic effect in various breast tumor models. Lately, it was found that cannabinoid treatment not only stimulates autophagy-mediated apoptotic death of tumor cells through unfolded protein response (UPRER) activated downstream effectors, but also imposes cell cycle arrest. The exploitation of UPRER tumors as such is believed to be a major molecular event and is therefore employed in understanding the development and progression of breast tumor. Simultaneously, the data on clinical trials following administration of cannabinoid is currently being explored to find its role not only in palliation but also in the treatment of breast cancer. The present study summarizes new achievements in understanding the extent of therapeutic progress and highlights recent developments in cannabinoid biology towards achieving a better cure of breast cancer through the exploitation of different cannabinoids.
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