The cytoplasmic domain of MT1-MMP is dispensable for migration augmentation but necessary to mediate viability of MCF-7 breast cancer cells

Cepeda, Mario; Pelling, Jacob J. H.; Evered, Caitlin L.; Leong, Hon S.; Damjanovski, Sashko

doi:10.1016/j.yexcr.2016.11.019

Cited by 6 publications

(12 citation statements)

References 60 publications

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“…MMPs, particularly MT1-MMP, are multifunctional proteases that regulate ECM degradation, pro-MMP-2 activation, and viability; importantly, the cytoplasmic domain of MT1-MMP is required for cell survival. 24 Here, the improved uptake of MATT by LTSLs might result in increased binding of MATT with the cytoplasmic domain of MT1-MMP, which subsequently affects cell viability.…”

Section: Resultsmentioning

confidence: 99%

Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis

Lyu

Xiao

Yin

et al. 2019

Sig Transduct Target Ther

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Metastasis is a major cause of chemotherapeutic failure and death. Degradation of a specific component of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) affects the physical barrier of the tumor microenvironment (TME) and induces metastasis. Here, lysolipid-containing thermosensitive liposomes (LTSLs) were prepared to deliver an MMP inhibitor, marimastat (MATT), to the TME to inhibit MMP activity and expression. LTSLs rapidly released their payloads at 42 °C. Compared with the saline control, MATT-LTSLs exhibited enhanced accumulation in the tumor and a 20-fold decrease in tumor growth in 4T1 tumor-bearing mice; moreover, MATT-LTSLs reduced MMP-2 and MMP-9 activity by 50% and 43%, respectively, and downregulated MMP-2 and MMP-9 expression in vivo by 30% and 43%, respectively. Most importantly, MATT-LTSL treatment caused a 7-fold decrease in metastatic lung nodules and a 6-fold reduction in microvessels inside the tumor. We believe this study provides an effective approach for the suppression of metastasis, and the use of a cytotoxic agent in combination with MATT is a potential strategy for metastatic cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis

Lyu

Xiao

Yin

et al. 2019

Sig Transduct Target Ther

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“…This is perhaps because unlike MCF-7 cells, where The relationship between cell line and vascularization was compared using a chi-squared test of independence; X 2 (1, N = 33) = 2.494, p = 0.114. The relationship between cell line and wound closure was compared using a chi-squared test of independence, and was statistically different; X 2 (1, N = 24) = 5.513, p = 0.019 increased MT1-MMP levels resulted in increased levels of transcription by NF-κB (Cepeda et al 2017b), here MDA-MB-231 cells with increased MT1-MMP levels resulted in decreased levels of transcription by NF-κB (Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

Stable expression of α1-antitrypsin Portland in MDA-MB-231 cells increased MT1-MMP and MMP-9 levels, but reduced tumour progression.

Willson

Muir

Evered

et al. 2017

J. Cell Commun. Signal.

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The membrane bound matrix metalloproteinase MT1-MMP plays roles in modulating cell movement, independent of its abilities to remodel the extracellular matrix. Unlike many MMPs, MT1-MMP is activated in the Golgi prior to secretion by a pro-protein convertase, primarily furin. Regulation of the activation of pro-MT1-MMP has been methodically investigated, as altering the level of the active protein has broad implications in both activating other pro-MMPs, including pro-MMP-2, and many subsequent remodelling events. Our previous work in MCF-7 cells has demonstrated that modest, and not extremely high, levels of active MT1-MMP manifests into altered cell morphology and movement. At this low but optimal amount of MT1-MMP protein, changes to MT1-MMP levels are always mirrored by MMP-9 and pERK levels, and always opposite to MMP-2 levels. In this study, stable expression of the furin inhibitor α1-antitrypsin Portland (α1-PDX) in MDA-MB-231 cells increased overall MT1-MMP levels, but cells maintained a 21% proportion of pro-MT1-MMP. The increase in MT1-MMP was mirrored by increases in MMP-9 and pERK, but a decrease in MMP-2. These changes were associated with increased NF-κB transcription. In vitro analysis showed that α1-PDX decreased cell protrusions and migration, and this manifested as decreased tumourigenesis when examined in vivo using a chick CAM assay.

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“…Interestingly, another experiment result revealed that MT1-MMP in the cytoplasmic domain was indispensable for migration but necessary to mediate viability of the MCF-7 breast cancer cell line [25],…”

Section: Discussionmentioning

confidence: 99%

The Prompting Effects of MT1-MMP on EMT in Breast Cancer

Zhang

et al. 2021

Preprint

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ObjectiveEpithelial to mesenchymal transition (EMT) was the initial process of invasion and metastasis leading to a relapse of breast cancer following resection and chemo-radiotherapy. Membrane type-1 Matrix Metalloproteinase (MT1-MMP) was confirmed to play an important role in EMT in various cancers. However, the MT1-MMP effects on EMT in breast cancer had not yet been studied. Here,We investigated the MT1-MMP effects on breast cancer EMTonset, invasion, and migration abilities in MCF-7 cells. MethodsExpressions of MT1-MMP and EMT-associated proteins including E-cadherin, N-cadherin, and Vimentin were detected by immunohistochemistry in 71 breast cancer resection samples. The relationships of MT1-MMP with clinic- pathological parameters were statistically analyzed, as well as EMT-associated proteins. Western blot tests were performed to test MT1-MMP and EMT-associated proteins expression levels in MCF-7 cells transfected by MT1-MMP plasmid. Wound-healing and transwell experiments were used to estimate MT1-MMP-induced invasion and migration. ResultsOverexpression of MT1-MMP was verified in 71 breast cancer patients. MT1-MMP levels were observed to be correlated with the breast cancer clinical TNM stage, lymph node metastasis, and tumor size. The EMT-associated proteins including N-cadherin and Vimentin expression levels were higher both in MT1-MMP strong positive breast cancer resection samples and MCF-7 cells transfected with MT1-MMP plasmid. Furthermore, MCF-7 cells also acquired more ability to migrate and invade according to the results of the wound-healing assays and transwell experiments.ConclusionMT1-MMP was overexpressed in breast cancer tissue, and MT1-MMP promoted breast cancer EMT incidence, which was closely associated with breast cancer invasion and migration.

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The cytoplasmic domain of MT1-MMP is dispensable for migration augmentation but necessary to mediate viability of MCF-7 breast cancer cells

Cited by 6 publications

References 60 publications

Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis

Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis

Stable expression of α1-antitrypsin Portland in MDA-MB-231 cells increased MT1-MMP and MMP-9 levels, but reduced tumour progression.

The Prompting Effects of MT1-MMP on EMT in Breast Cancer

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