Clinical and prognostic role of matrix metalloproteinase-2, -9 and their inhibitors in breast cancer and liver diseases: A review

Daniele, Antonella; Abbate, I.; Oakley, Clare; Casamassima, Porzia; Savino, Eufemia; Casamassima, A.; Sciortino, Giancarlo; Fazio, V De; Gadaleta-Caldarola, Gennaro; Catino, Annamaria; Giotta, Francesco; Luca, Raffaele De; Divella, Rosa

doi:10.1016/j.biocel.2016.06.002

Cited by 45 publications

(42 citation statements)

References 62 publications

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“…The above observations led us to focus on MMP2 and MMP9, both of which are involved in cellular invasiveness and cancer metastasis . First, we observed that MMP9 mRNA, unlike MMP2 mRNA, was increased in HIC‐5–silenced cells, suggesting a role of HIC‐5 in the regulation of MMP9 expression (Fig.…”

Section: Resultsmentioning

confidence: 86%

A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and invasive properties in RAS‐activated cancer cells

et al. 2018

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Matrix metalloproteinases (MMPs) are tissue‐remodeling enzymes involved in the processing of various biological molecules. MMPs also play important roles in cancer metastasis, contributing to angiogenesis, intravasation of tumor cells, and cell migration and invasion. Accordingly, unraveling the signaling pathways controlling MMP activities could shed additional light on cancer biology. Here, we report a molecular axis, comprising the molecular adaptor hydrogen peroxide‐inducible clone‐5 (HIC‐5), NADPH oxidase 4 (NOX4), and mitochondria‐associated reactive oxygen species (mtROS), that regulates MMP9 expression and may be a target to suppress cancer metastasis. We found that this axis primarily downregulates mtROS levels which stabilize MMP9 mRNA. Specifically, HIC‐5 suppressed the expression of NOX4, the source of the mtROS, thereby decreasing mtROS levels and, consequently, destabilizing MMP9 mRNA. Interestingly, among six cancer cell lines, only EJ‐1 and MDA‐MB‐231 cells exhibited upregulation of NOX4 and MMP9 expression after shRNA‐mediated HIC‐5 knockdown. In these two cell lines, activating RAS mutations commonly occur, suggesting that the HIC‐5–mediated suppression of NOX4 depends on RAS signaling, a hypothesis that was supported experimentally by the introduction of activated RAS into mammary epithelial cells. Notably, HIC‐5 knockdown promoted lung metastasis of MDA‐MB‐231 cancer cells in mice. The tumor growth of HIC‐5–silenced MDA‐MB‐231 cells at the primary sites was comparable to that of control cells. Consistently, the invasive properties of the cells, but not their proliferation, were enhanced by the HIC‐5 knockdown in vitro. We conclude that NOX4‐mediated mtROS signaling increases MMP9 mRNA stability and affects cancer invasiveness but not tumor growth.

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Section: Resultsmentioning

confidence: 86%

A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and invasive properties in RAS‐activated cancer cells

et al. 2018

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“…Upregulation of MMPs contributes to ECM remodeling, tumor cell invasion and metastasis, leading to the development of malignancies . An upregulation of MMP‐2 and MMP‐9 expression and activity has been shown to play a key role in many human cancers with metastatic capability . Both mRNA and serum levels of MMP‐2 and MMP‐9 have been found to be overexpressed in liver diseases and HCC .…”

Section: Discussionmentioning

confidence: 99%

β‐mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP‐2 and MMP‐9 expression and activating the ERK and JNK pathways

Huang

Teng

et al. 2017

Environmental Toxicology

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β-mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of β-mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that β-mangostin did not induce cytotoxicity in human HCC cells (SK-Hep-1, Huh-7 and HA22T/VGH cells). β-mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, β-mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP-2/-9 and invasion by β-mangostin treatment in Huh-7 cells. In addition, β-mangostin effectively restored the protein levels and transcription activity of MMP-2 and MMP-9 in siERK or siJNK-transfected Huh-7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of β-mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC.

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“…MMP2 and MMP9 are involved in ECM remodeling and vascular smooth muscle cell proliferation (Figure S3, Supporting Information). Gelatinases’ activity is selectively regulated by distinct TIMPs, with TIMP‐2 showing higher affinity to MMP2 and TIMP‐1 to MMP9 . Accordingly, STRING v10.5 network analysis of the ten MMPs involved in the modeling of body fluids peptidome highlights TIMPs as a common denominator (Figure S4, Supporting Information).…”

Section: Comparative Analysis Of Proteases Distribution Among Distincmentioning

confidence: 98%

Reviewing Mechanistic Peptidomics in Body Fluids Focusing on Proteases

et al. 2018

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The comprehension of how protease networks sculpt proteomes might help to disclose the functional annotation of the peptidome in health and disease. Envisioning to add new insights on the protease networks involved in the regulation of body fluid peptidomes, the authors apply Proteasix software to predict the proteases involved in the generation of the naturally occurring peptides present in six of the most studied human body fluids. Peptidome data is collected from the databases and from experimental studies. The analysis highlights 132 putative proteases from four families with the predominance of serine proteases and metalloproteases. From these, 49 proteases seem to be common to all fluids and are mostly associated to extracellular matrix organization as well as protein/peptide hormone processing. Data analysis also emphasizes: i) the similarity between plasma and CSF protease profiles; ii) that saliva and tears share proteases involved in the generation of peptides with antimicrobial activity; iii) that urine is the body fluid with the highest number of unique putative proteases, precluding an easy tracing of proteolytic events in this case. Taken together, the analysis emphasizes the intricate modus operandi of proteases, challenged by the interconnected pathways and amplification cascades in which they are involved.

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Clinical and prognostic role of matrix metalloproteinase-2, -9 and their inhibitors in breast cancer and liver diseases: A review

Cited by 45 publications

References 62 publications

A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and invasive properties in RAS‐activated cancer cells

A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and invasive properties in RAS‐activated cancer cells

β‐mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP‐2 and MMP‐9 expression and activating the ERK and JNK pathways

Reviewing Mechanistic Peptidomics in Body Fluids Focusing on Proteases

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