Focal adhesion kinase (FAK) is a widely expressed cytoplasmic protein tyrosine kinase involved in integrin-mediated signal transduction. It plays an important role in the control of several biological processes, including cell spreading, migration, and survival. Activation of FAK by integrin clustering leads to autophosphorylation at Tyr397, which is a binding site for the Src family kinases PI3K and PLCγ.
The extracellular matrix (ECM) is a three-dimensional macromolecular network composed of collagens, proteoglycans, glycosaminoglycans, elastin, fibronectin, laminins, along with many other proteins and glycoproteins. This network of macromolecules provides a dynamic microenvironment that supports cell and tissue function, and undergoes continuous remodeling during both normal development and disease.
Exosomes are membrane-wrapped extracellular vesicles (EVs) with a diameter of approximately 40-160 nm, possessing a lipid bilayer structure. They are naturally present in blood, urine, cerebrospinal fluid, and the supernatant of cultured cells in vitro, and almost all types of cells can produce and release exosomes.
Endoplasmic Reticulum Stress Secretory and transmembrane proteins are synthesized on polysomes and translocate into the endoplasmic reticulum (ER) where they are often modified by the formation of disulfide bonds, amino-linked glycosylation and folding. The ER contains a pool of molecular chaperone proteins including calnexin, BiP and protein disulfide isomerase (PDI).
Estrogen receptor α (ERα), a member of the steroid receptor superfamily, contains highly conserved DNA binding and ligand binding domains. Through its estrogen-independent and estrogen-dependent activation domains (Estrogen receptor αAF-1 and AF-2, respectively), ERα regulates transcription by recruiting coactivator proteins and interacting with general transcriptional machinery. Phosphorylation at multiple sites provides an important mechanism to regulate ERα activity.
Epithelial-mesenchymal transition (EMT) is an essential process during development whereby epithelial cells acquire mesenchymal, fibroblast-like properties and display reduced intracellular adhesion and increased motility. This is a critical feature of normal embryonic development, which is also utilized by malignant epithelial tumors to spread beyond their origin.
Mitochondria are the main site for ATP production in animal and plant cells, and are important organelles that promote cellular energy conversion and participate in cell apoptosis. Mitochondria store the energy generated during respiratory oxidation in the inner membrane of mitochondria as electrochemical potential energy, causing asymmetric distribution of proton and other ion concentrations on both sides of the inner membrane and forming the mitochondrial membrane potential (MMP, Δ PSI m). Normal MMP is a prerequisite for maintaining mitochondrial oxidative phosphorylation and producing adenosine triphosphate. The stability of MMP is beneficial for maintaining normal physiological functions of cells.
Endosomes are formed by the invagination of the plasma membrane to form vesicles in an effort to recycle components of the cell (1). Endosomes can be coated in clathrin when vesicles form at clathrin-coated pits (2). Caveolins are 21-24 kDa integral proteins that interact with cholesterol and are the main structural components of the cholesterol/sphingolipid-enriched plasma membrane caveolae (3). Each stage of endosome maturation is marked by a unique set of proteins. EEA1 is an early endosome marker that is essential for membrane fusion and trafficking (4). Members of the ras superfamily of small Rab GTPases, specifically Rab5, Rab7, and Rab11 are markers of the early, late and recycling endosomes (5).
Mitochondrial acyl carrier protein (ACP) is an essential component in fatty acid biosynthesis in mitochondria. It is also known as NADH-ubiquinone oxidoreductase subunit AB1 (NDUFAB1), a Complex I subunit in the electron transport chain (ETC). NDUFAB1 regulates energy and reactive oxygen species (ROS) metabolism in mitochondria by coordinating the assembly of ETC Complexes I, II, and III, and supercomplexes (1). NDUFS1 (NADH dehydrogenase Fe-S protein 1) is a nuclear-encoded structural subunit of NADH: ubiquinone oxidoreductase (Complex I) in the mitochondrial ETC (2). Mutations in NDUFS1 and other Complex I subunits leading to mitochondrial dysfunction are associated with a number of neurological disorders (3-6).
The extracellular matrix (ECM) is a cell surface associated three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. The network provides a dynamic microenvironment surrounding the cell enabling it to carry on its function.
