mTOR Signaling and the Tumor Microenvironment

Multifaceted Roles of Matrix Metalloproteinase-2 (MMP2) in Normal and Disease State

MMP2 is a 72 kDa enzymatic protein and it belongs to matrix metalloproteinases (MMPs), a heterogenous family of zinc/calcium-dependent TIMPs (tissue inhibitors of matrix metalloproteinases) regulated matrix-degrading endopeptidases which are classified into collagenases (MMP-1, -8, -13, -18), gelatinases (MMP-2, -9), stromelysins (MMP-3, -7, -10, -11), elastase (MMP-12), and membrane-type matrix metalloproteinases (MT-MMP-1 through -5) (1). MMP2 involves in extracellular matrix metabolism and cleaves type IV collagen along with degrading the already denatured collagens.

Integrin alpha v beta 3 - a target for inhibiting tumor angiogenesis

Integrins are a family of transmembrane proteins involved in diverse processes including cell adhesion, signal transduction, cell migration, and differentiation. They exist as heterodimers consisting of noncovalently linked alpha and beta subunits. Integrin complexes span the plasma membrane and link the cytoskeleton with the extracellular matrix. In mammals there are 18 alpha and 8 beta subunits that can assemble into 24 distinct integrin heterodimers with alternative splicing adding even more diversity.

Integrin Beta 1/CD29 - a cell adhesion and cell signaling protein with diverse functions

Integrins are a large family of trasmembrane proteins involved in cell adhesion and form a link between the intracellular cyskeletal proteins and extracellular matrix proteins. Integrins exist as heterodimers consisting of alpha and beta subunits. In addition to cell adhesion these integrin complexes play key roles in diverse processes such as signal transduction, cell migration, proliferation, differentiation, and apoptosis. Integrins consist of three domains: the extracellular domain, the transmembrane domain, and the cytoplasmic tail.

Beta-defensin-3: I may be small but I'm powerful!

Beta-defensin 3 is a novel, non-hemolytic antimicrobial cationic peptide originally isolated from human lesional psoriatic scales and keratinocyte clones. It is a very small (2-6 kD) yet potent salt-insensitive broad spectrum antimicrobial that targets many pathogenic microbes such as multiresistant S. aureus, vancomyosin-resistant Enterococcus faecium, Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses.

VEGFR-2 - A highly active kinase

VEGFR-2 is a family member of the vascular endothelial growth factor (VEGF) family of membrane receptor tyrosine kinases. It is a key regulator of the process of angiogenesis that takes place during fundamental developmental processes such as embryogenesis, skeletal growth, and reproductive functions. Like other growth factor receptors, upon ligand binding, VEGFR2 dimerizes and is autophosphorylated on multiple tyrosine residues.

MMP24 (Matrix metalloproteinase-24, matrix metalloproteinase-25, MT5-MMP)

MMP24 is an extracellular matrix (ECM) degradative peptidase enzyme that is a member of the large family of matrix metalloproteinases (MMP). Each MMP has a different substrate specificity, and the aberrant or derailed expression of these is strongly correlated with unregulated events such as tumor invasion, metastasis, angiogenesis, and arthritis. This is in contrast to the tightly controlled normal physiological processes such as tissue remodeling, reproduction, rebuilding, and embryonic development. Deregulation often occurs through the loss of negative checks.

VEGF: Vascular endothelial growth factor

VEGF is homodimeric, disulfide-linked glycoprotein cytokine that serves as the ligand for FLT1 (VEGFR-1 receptor) and FLK1 (VEGFR-2 receptor) tyrosine kinases. It is a key modulator of physiological angiogenesis, vasculogenesis, and endothelial cell growth during basic developmental processes such as embryogenesis, skeletal growth, and reproductive functions.

Factor VII - A Major Protein in Blood Coagulation

Factor VII (coagulation factor VII) is a 50 kD multidomain single chain plasma glycoprotein synthesized in the liver. It is a vitamin K-dependent serine protease essential for the extrinsic pathway of hemostasis, or blood coagulation. Factor VII circulates in the blood in a zymogen form that is converted to an active form (via factor IXa, factor Xa, factor XIIa, or thrombin).

MMP2: The extracellular matrix bids you adieu

MMP2 is a peptidase enzyme that belongs to the large family of matrix metalloproteinases (MMPs) which degrade the extracellular matrix (ECM) with different substrate specificities. Aberrant and unregulated expression of MMPs via deregulation of key negative check controls is strongly associated with increased tumor invasiveness, metastasis potential, and angiogenesis. This uncontrolled behavior is in direct contrast to the tightly controlled physiological systems of embryonic development, tissue remodeling, and rebuilding.