Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis

Abstract

The purpose of this review is to highlight the recent mechanistic developments elucidating the role of matrix metalloproteinases (MMPs) in tumour invasion and metastasis. The ability of tumour cells to invade, migrate, and subsequently metastasize is a fundamental characteristic of cancer. Tumour invasion and metastasis are increasingly being characterized by the dynamic relationship between cancer cells and their microenvironment and developing a greater understanding of these basic pathological mechanisms is crucial. While MMPs have been strongly implicated in these processes as a result of extensive circumstantial evidence -for example, increased expression of individual MMPs in tumours and association of specific MMPs with prognosis -the underpinning mechanisms are only now being elucidated. Recent studies are now providing a mechanistic basis, highlighting and reinforcing the catalytic and non-catalytic roles of specific MMPs as key players in tumour invasion and metastasis.

Role and molecular mechanism of heterogeneous nuclear ribonucleoprotein K in tumor development and progression

“…These factors have an important role in promoting tumor metastasis. A succession of studies are now providing a mechanistic basis, highlighting and reinforcing that specific MMPs are key in tumor invasion and metastasis through their catalytic and non-catalytic roles, including modulating tumor cell motility, promoting invadopodia formation, interactions of MMPs with pro-invasive pathways, sensing matrix stiffness and induction and maintenance of epithelial-mesenchymal transition (44). Therefore, hnRNP K simultaneously provided favorable conditions for tumor invasion and metastasis when upregulating MMPs expression.…”

Inhibitory effect of aminoethyl-chitooligosaccharides on invasion of human fibrosarcoma cells

“…The cause of death caused by cancer is identified to be due to invasion and metastasis (Brown and Murray, 2015). In general, metastasis occurs when the unstable cells surrounding tumor in tissue environment.…”

Cancer cell behaviors mediated by dysregulated pH dynamics at a glance

“…Decreased pH e enables cell migration (Stock and Schwab, 2009;Stock et al, 2005) and invasion (Estrella et al, 2013), in part by increasing the activity of acid-activated matrix metalloproteinases (MMPs) that dissolve cell-substrate adhesions (Brown and Murray, 2015;Yamamoto et al, 2015). Evidence suggests that NHE1 is a significant contributor to matrix degradation through local extracellular acidification or effects on MMP expression and localization (Lin et al, 2012;Putney and Barber, 2004).…”

“…We refer generally to cytosolic pH i , but the pH of various organelles is distinct from cytosolic pH (for review, see Casey et al, 2010) and cytosolic pH can be different in distinct parts of the cell, such as at lamellipodia (Stock et al, 2007) and invadopodia (Beaty et al, 2014). While the decreased pH e of cancer cells will be briefly discussed -as it relates to pH i and its role in enabling cell migration -detailed reviews on how decreased pH e alters cell-matrix remodeling can be found elsewhere (Stock and Schwab, 2009;Brown and Murray, 2015;Yamamoto et al, 2015;Hashim et al, 2011). Where known, we discuss the role of specific pH-sensors in the pH i -dependent cell process and molecular mechanisms for pH sensing.…”