Seesaw of matrix metalloproteinases (MMPs)

Abstract

The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumor progression and the metastatic process by facilitating extracellular matrix (ECM) degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by MMP inhibitors (MMPIs) have rapidly developed. This paper reviews MMPs in detail. Their perspectives in therapeutic intervention in cancer are also mentioned.

Role of matrix metalloproteinase-9 in transforming growth factor-β1-induced epithelial–mesenchymal transition in esophageal squamous cell carcinoma

“…The expression and activity of MMPs were shown to be increased in almost every type of human cancer; and this increase was shown to correlate with the advanced tumor stage, increased invasion and metastasis, and shortened survival 20. MMP-9, also known as gelatinase B, plays a critical role in the processes that represent the hallmarks of cancer, including migration, invasion, and angiogenesis 39–41.…”

“…MMPs represent a family of zinc-containing proteolytic enzymes that break down the protein components of the extracellular matrix (ECM) and endothelial cell basement membrane 18. MMPs and their specific inhibitors (TIMPs) play an important role in the progression of different types of solid and hematological malignancies by regulating cell growth, cancer cell activation, and immune functions 19,20. In addition to the ability of MMPs to remodel ECM, some of these molecules, such as MMP-3, MMP-9, MMP-14, and MMP-28, are known to induce EMT directly 21–25.…”

Silencing of gelatinase expression delays myoblast differentiation in vitro

“…Soon after muscle injury these cells become activated and resume the cell cycle becoming myoblasts, which align and fuse to reconstruct multinuclear myofibers. According to their substrate specificity MMPs are classified into five classes: collagenases (MMP-1, , gelatinases (MMP-2 and MMP-9), stromelysins (MMP-3, MMP-10, and MMP-11), membrane-anchored MMPs , and a heterogeneous group named "other MMPs" (Alameddine, 2012;Apte and Parks, 2015;Kapoor et al, 2016). Importantly, satellite cell activation and myoblast differentiation is precisely controlled by sequentially expressed muscle specific transcription factors-Myf5, MyoD, and myogenin, as well as structural proteins, such as myosin heavy chains (MyHC).…”

The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke

“…At least twenty-five different MMPs have been identified [29]. Members of this protease family have been divided into five subclasses based on structural similarity and substrate specificity that include the following: collagenases (MMP-1, MMP-8, and MMP-13) [30,31,32], gelatinases (MMP-2 and MMP-9) [33,34,35], stromelysins (MMP-3 and MMP-10) [36,37], metalloelastases [38,39], membrane-type MMPs (MT-MMP, MMP-14, MMP 15, MMP-16, MMP-17, MMP-24, and MMP-25) [40,41,42,43,44,45], and others (MMP-7, MMP-11, MMP-12, MMP-19, MMP-20 and MMP-23) [46,47].…”