Cancer

The protein ATF6 is a constitutively expressed transcription factor that is a key mediator of the unfolded protein response (UPR) that allows mammalian cells to maintain cellular homeostasis under conditions of environmental and physiological stress. ATF6 is endoplasmic reticulum (ER) membrane-anchored in its inactive form, and under certain stress conditions, translocates to the Golgi where it is processed into its active form through action of the S1P and S2P proteases.

The CIP2A protein was originally identified as p90, a cytoplasmic auto-antigen from the serum of a cancer patient. It was later found to inhibit protein phosphatase 2A (PP2A) activity as well as interact with c-myc. CIP2A's inhibitory activity blocks c-myc phosphorylation and its subsequent proteolytic degradation, producing a stable c-myc that promotes aberrant cell growth and transformation. In addition to its role in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation.

The enzyme S-adenosylmethionine synthetase, or MAT, catalyzes the formation of S- adenosylmethionine (AdoMet or SAMe) from methionine and ATP. AdoMet is the principal biological source of synthesized methyl, and is found in all cells but most prominently in the liver. In mammalian tissues, there are three distinct AdoMet synthases - the alpha, beta, and gamma isoforms. While the alpha and beta variants are uniquely expressed solely in the adult liver, gamma is more widely distributed in the extrahepatic tissues.

The protein, carbonic anhydrase IX, belongs to the carbonic anhydrase family which consists of enzymes that rapidly convert carbon dioxide and water into the end products of carbonic acid, protons, and bicarbonate ions. These enzymes play a widespread role in cells by regulating the pH of normal tissues, and are abundantly expressed in all mammalian tissues. Due to its stability and membrane location, CAIX is one of the most hypoxically-inducible genes, and has become a reliable hypoxia histochemical marker.

Also known as OPG, TR1 and OCIF, this gene encodes Osteoprotegerin, a heparin-binding secretory glycoprotein that belongs to the TNF-receptor superfamily. The TNFR superfamily consists primarily of transmembrane proteins that elicit signal transduction in a variety of cells and are known to mediate diverse biological responses, including cytotoxicity and apoptosis, Osteoprotegerin (OPG) was isolated independently by two laboratories in 1997 [1,2].

ASC-2, also known as Nuclear Receptor Co-Activator 6, directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. It is involved in the co-activation of different nuclear receptors, such as for steroids (GR and ERs), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). It is believed to function as a general co-activator, rather than just a nuclear receptor co-activator.

LYVE1 (lymphatic vessel endothelial hyaluronan receptor-1) is one of the most specific and widely used mammalian lymphatic endothelial markers.It is found in lymph nodes and at the luminal/abluminal surfaces of lymphatic vessels. It is a single-pass type I membrane protein that exists in a disulfide-linked homodimer form. LYVE1 undergoes ligand-dependent internalization and recycling at the cell surface, and exhibits ligand-specific transporter trafficking between intracellular organelles and the plasma membrane.

Macrophage mannose receptor 1 (MRC1), also known as CD206, is a Pattern Recognition Receptor (PRR). PRRs are expressed by antigen processing and presentation cells, and are activated upon detection of Pathogen-Associated Molecular Patterns (PAMPs). PAMPs are molecular sequences shared by large groups of pathogens, which are essential for microbial survival and/or pathogenicity and include cell wall components such as glycoproteins.

LOX is a copper-dependent amine oxidase enzyme that executes post-translational oxidative deamination on peptidyl lysine residues in precursors of fibrous collagen and elastin. LOX is secreted into the extracellular environment in an inactive form, where it is processed into an active form. Its activity is crucial for maintaining both the tensile and elastic properties of connective tissue residing within skeletal, pulmonary, and cardiovascular systems.

LAMP2 belongs to the family of membrane glycoproteins who confer selectins with carbohydrate ligands. LAMP2 has been implicated in tumor cell metastasis, as well as overall protection, maintenance, and adhesion of the lysosome. It appears that LAMP2 may protect the lysosomal membrane from autophagy, as well as maintain the required acidic environment necessary for proper function.  LAMP2 is a single-pass type I membrane protein that shuttles between endosomes, lysosomes, and the plasma membrane.