E-Cadherin

By Jamshed Arslan, Pharm. D., PhD.

Cathepsins are a family of lysosomal proteases (serine, aspartic and cysteine proteases) that acts in conjunction with lipases and nucleases to degrade biological macromolecules in the lysosomes (1). While most cathepsins are ubiquitously expressed to support normal lysosomal degradation, cathepsin B is unique for its role in various pathologies and malignancies (2). Cathepsin B is often overexpressed and alternatively spliced in cancer cells (2).

The SOX gene family encodes a group of highly conserved transcription factors defined by the presence of a conserved high motility group (HMG) DNA-binding domain. They are involved in embryonic development regulation and cell fate determination. All SOX proteins have a single HMG box and bind linear DNA in a sequence-specific manner, resulting in the bending of DNA through large angles. This bending opens the DNA helix for some distance, which may affect the binding and interactions of other transcription factors.

Beta-catenin is a cytosolic, 88 kDa intracellular protein associated with cell surface cadherin glycoproteins. It is a member of the larger calcium-dependent catenin family that includes alpha-catenin, beta-catenin, and gamma-catenin (also known as plakoglobin). Beta-catenin enters the nucleus to interact with TCF/LEF (Lymphoid enhancer factor-1) transcription factor family. It is normally inhibited by the GSK (glycogen synthase kinase) or CK1 (casein kinase 1) as phosphorylation of beta-catenin targets it for ubiquitin-mediated degradation.

Vimentin, a member of the intermediate filament (IF) family, is a protein responsible for maintaining cellular integrity and reducing damage caused by stress.

Carbonic anhydrase IX (CAIX) is a membrane-associated carbonic anhydrase, strongly induced by hypoxia. CA IX is overexpressed by several cancer cells from many tumor types, and is a component of the pH regulatory system invoked by these cells to combat the deleterious effects of a high rate of glycolytic metabolism.

E-cadherin is a calcium-regulated adhesion molecule expressed in most normal epithelial tissues. E-cadherin is also associated with gland formation, stratification, and epithelial polarization, while loss of E-cadherin can cause dedifferentiation and invasiveness in several human carcinomas (1). In a recent study, human breast cancer tissues were stained immunohistochemistry (IHC) by anti- E-Cadherin antibodies.

E-Cadherin is a member of the cadherin superfamily and is fundamental player in a wide range of cellular processes such as development, morphology, polarity, migration and tissue integrity. Specifically, E-cadherin is an approximately 100 kDa epithelial cell glycoprotein whose extracellular domain interacts with that of other E-cadherin molecules on adjacent cells to establish cell-cell adhesion. This adhesion is Ca^2+-dependent and a variety of interactions have been identified.