Calpain-mediated Mechanoptosis in Breast Adenocarcinoma.

Calpains belong to a family of important calcium-dependent cysteine proteases. They are involved in intracellular processes including cytoskeleton disorganization and substrate proteolysis. They also enhance apoptosis and cell to cell adhesion. Calpains demonstrate also a mechanosensory function in neoplastic and malignant cells due to their implication in mechanoptosis. This is a specific type of apoptotic death induced by strong external mechanical stimuli. Anti-cytoskeleton rigidity inhibition strategies based on calpain induction lead to increased apoptosis of tumor transformed cells. Elevated intracellular calcium concentration mediated by specific receptors and channels activates calpains. In the current molecular review, we explored the role of calpains in calcium-dependent signa transduction pathways in breast adenocarcinoma in conjunction with novel agents that activate their important anti-tumor functions.

DNA Mismatch Repair System Imbalances in Breast Adenocarcinoma.

DNA mismatch repair system (MMR) is considered a leading genetic mechanism in stabilizing DNA structure and maintaining its function. DNA MMR is a highly conserved system in bacteria, prokaryotic, and eukaryotic cells, and provides the highest protection to DNA by repairing micro-structural alterations. DNA MMR proteins are involved in the detection and repair of intra-nucleotide base-to-base errors inside the complementary DNA strand recognizing the recently synthesized strand from the parental template. During DNA replication, a spectrum of errors including base insertion, deletion, and miss-incorporation negatively affect the molecule's structure and its functional stability. A broad spectrum of genomic alterations such as promoter hyper methylation, mutation, and loss of heterozygosity (LOH) in MMR genes including predominantly hMLH1, hMSH2, hMSH3, hMSH6, hPMS1, and hPMS2 lead to their loss of base-to-base error repairing procedure. Microsatellite instability (MSI) refers to the DNA MMR gene alterations that are observed in a variety of malignancies of different histological origins. In the current review, we present the role of DNA MMR deficiency in breast adenocarcinoma, a leading cancer-based cause of death in females worldwide.

Epigenetic Mechanisms in Breast Adenocarcinoma: Novel DNA Methylation Patterns.

Breast adenocarcinoma is a leading cause of death in females worldwide. A broad spectrum of genetic and epigenetic alterations has been already identified and reported in millions of examined cancerous substrates, evidence of a high-level genomic heterogeneity that characterizes these malignancies. Concerning epigenetic changes and imbalances that critically affect progression and prognosis in the corresponding patients, DNA methylation, histone modifications (acetylation), micro-RNAs (miRs) alterations and chromatin re-organization represent the main mechanisms. Referring to DNA methylation, promoter hyper-hypo methylation in critical tumour suppressor and oncogenes is implicated in normal epithelia transformation to their neoplastic and finally malignant cyto-phenotypes. The current review is focused on the different methylation patterns and mechanisms detected in breast adenocarcinoma and their impact on the corresponding groups of patient response to specific chemotherapeutic regimens and life span prognosis.