EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

Paye, Alexandra; Truong, Alice; Yip, Cassandre; Cimino, Jonathan; Blacher, Silvia; Munaut, Carine; Cataldo, Didier; Foidart, Jean Michel; Maquoi, Erik; Collignon, Joëlle; Delvenne, Philippe; Jérusalem, Guy; Noël, Agnès; Sounni, Nor Eddine

doi:10.1158/0008-5472.can-13-2994

Cited by 39 publications

(66 citation statements)

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“…Previous studies have shown that MT4 promotes tumor growth and metastasis and influences cell proliferation. Pave et al [43] reported that MT4 promotes cancer cell proliferation in vivo and in vitro by promoting an outside-in signaling through the EGFR pathway. Based on this information, the differentially miRNAs evaluated in the present study may be involved in cell proliferation, differentiation, and apoptosis, as well as the growth and development of hair follicles in Hu sheep lambskin.…”

Section: Discussionmentioning

confidence: 99%

Screening candidate microRNAs (miRNAs) in different lambskin hair follicles in Hu sheep

et al. 2017

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Hu sheep lambskin is a unique white lambskin from China that exhibits three types of flower patterns, including small waves, medium waves, and large waves, with small waves considered the best quality. However, our understanding of the molecular mechanism underlying flower pattern formation in Hu sheep lambskin is limited. The aim of the present study was to further explore the relevance between candidate microRNAs (miRNAs) and developmental characteristics of hair follicles and screen miRNAs for later functional validation. Herein, we employed Illumina Hiseq 2500 to identify differentially expressed miRNAs in hair follicles of different flower patterns with small, medium, and large waves to construct a comprehensive sequence database on the mechanism of hair follicle development. Paraffin sections of lambskin tissue were prepared to assess the structure of different hair follicles. Expression levels of candidate miRNAs in different flower patterns were analyzed by relative quantitation using real-time PCR, combined with histological observation and micro-observation technologies, and the correlation between expression levels of candidate miRNAs and histological properties of hair follicles was analyzed by using SPSS 17.0. A total of 522 differentially expressed miRNAs were identified, and RNA-seq analysis detected 7,266 target genes in different groups of flower patterns. Gene ontological analysis indicated these target genes were mainly involved in cell proliferation, differentiation, growth, apoptosis, and ion transport, and 14 miRNAs, including miR-143, miR-10a, and let-7 were screened as candidate miRNAs in Hu sheep hair follicle growth and development. In the same field of vision, variance analysis showed that the number of secondary follicles in small waves was significantly larger than that in large and medium waves (P<0.01); the diameter of the primary and secondary follicles in large waves was respectively larger than those in medium and small waves (P<0.01). Combined with correlation analysis between miRNA expression and histological properties of hair follicles, highly significant differences in miRNA-143 expression levels between large and small waves were observed (P<0.01), and significant differences in the miRNA-10a expression levels between large and small waves (P<0.05) and in let-7i expression levels between large and medium waves were observed (P<0.05). Significant differences in the expression of novel miRNAs of NW_004080184.1_6326 between medium and large waves were detected (P<0.05), and highly significant differences between medium and small waves were observed (P<0.01). Highly significant differences in the expression level of NW_004080165.1_8572 between medium and large and small waves (P<0.01), in that of NW_004080181.1_3961 between medium and small waves (P<0.01), and in that of NW_004080190.1_13733 between medium and large waves were observed, whereas no significant differences in the other miRNAs among large, medium, and small waves were detected. Overall, the present study showed th...

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Section: Discussionmentioning

confidence: 99%

Screening candidate microRNAs (miRNAs) in different lambskin hair follicles in Hu sheep

et al. 2017

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“…We have recently identified the membrane type-4 matrix metalloproteinase (MT4-MMP or MMP17) as a new EGFR partner (Paye et al , 2014). Membrane type-4 matrix metalloproteinase belongs to the family of MT MMP that are tethered to the cell membrane through a trans-membrane domain (MT1-MMP, MT2-MMP, MT3-MMP and MT5-MMP) or a glycosylphosphatidylinositol anchor (MT4-MMP and MT6-MMP).…”

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“…Although the involvement of MMPs in cancer progression is well recognised and documented (Kessenbrock et al , 2010; Noel et al , 2012), only a few clinical and experimental studies report on MT4-MMP roles in cancer. Among the MMP family, MT4-MMP displays unique features and contributes to different steps of cancer progression through proteolytic and non-proteolytic functions (Chabottaux et al , 2006, 2009; Host et al , 2012; Paye et al , 2014). Membrane type-4 matrix metalloproteinase internalisation and recycling rely on a unique CLIC/GEEK pathway dependent on cdc-42 (Truong et al , 2016).…”

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confidence: 99%

“…Membrane type-4 matrix metalloproteinase internalisation and recycling rely on a unique CLIC/GEEK pathway dependent on cdc-42 (Truong et al , 2016). In an experimental setting, MT4-MMP overexpression stimulated tumour growth, angiogenesis and lung metastases (Chabottaux et al , 2006, 2009; Paye et al , 2014). The MT4-MMP impact on haematogenous metastatic dissemination is related to its capacity to remodel blood vasculature in a proteolytic-dependent manner (Host et al , 2012).…”

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confidence: 99%

“…In line with these findings, MT4-MMP has also been reported to play a significant role in hypoxia-mediated metastasis and to be an important prognostic indicator in patients with head and neck or gastric cancer (Huang et al , 2009; Wang et al , 2015). Beyond promoting cell invasiveness, MT4-MMP overexpression also endows TNBC cells with a higher proliferation rate (Paye et al , 2014). Indeed, in a non-proteolytic manner, MT4-MMP interferes with the EGFR pathway and promotes EGFR activation in response to its ligands.…”

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MT4-MMP and EGFR expression levels are key biomarkers for breast cancer patient response to chemotherapy and erlotinib

et al. 2017

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Background:Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a membrane type matrix metalloproteinase that interacts with epidermal growth factor receptor (EGFR) overexpressed in >50% of TNBC.Methods:We conducted a retrospective immunohistochemical analysis on human TNBC samples (n=81) and validated our findings in in vitro and in vivo assays.Results:Membrane type-4 matrix metalloproteinase and EGFR are produced in 72.5% of TNBC samples, whereas those proteins are faintly produced by healthy tissues. Unexpectedly, tumour relapse after chemotherapy was reduced in samples highly positive for MT4-MMP. Mechanistically, this is ascribed to a higher sensitivity of MT4-MMP-producing cells to alkylating or intercalating chemotherapeutic agents, as assessed in vitro. In sharp contrast, MT4-MMP expression did not affect tumour cell sensitivity to paclitaxel that interferes with protease trafficking. Importantly, MT4-MMP expression sensitised cancer cells to erlotinib, a tyrosine kinase EGFR inhibitor. In a pre-clinical model, the growth of MT4-MMP overexpressing xenografts, but not of control ones, was reduced by epirubicin or erlotinib. The combination of suboptimal drug doses blocked drastically the growth of MT4-MMP-producing tumours.Conclusions:We demonstrate that MT4-MMP defines a sub-population of TNBC sensitive to a combination of DNA-targeting chemotherapeutic agents and anti-EGFR drugs.

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Emerging roles of MT‐MMPs in embryonic development

Moracho

Learte

Muñoz-Sáez

et al. 2021

Developmental Dynamics

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Membrane-type matrix metalloproteinases (MT-MMPs) are cell membrane-tethered proteinases that belong to the family of the MMPs. Apart from their roles in degradation of the extracellular milieu, MT-MMPs are able to activate through proteolytic processing at the cell surface distinct molecules such as receptors, growth factors, cytokines, adhesion molecules and other pericellular proteins. Although most of the information regarding these enzymes comes from cancer studies, our current knowledge about their contribution in distinct developmental processes occurring in the embryo is limited. In this review, we want to summarize the involvement of MT-MMPs in distinct processes during embryonic morphogenesis, including cell migration and proliferation, epithelialmesenchymal transition, cell polarity and branching, axon growth and navigation, synapse formation, and angiogenesis. We also considered information about MT-MMP functions from studies assessed in pathological conditions and compared these data with those relevant for embryonic development.

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EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

Cited by 39 publications

References 49 publications

Screening candidate microRNAs (miRNAs) in different lambskin hair follicles in Hu sheep

Screening candidate microRNAs (miRNAs) in different lambskin hair follicles in Hu sheep

MT4-MMP and EGFR expression levels are key biomarkers for breast cancer patient response to chemotherapy and erlotinib

Emerging roles of MT‐MMPs in embryonic development

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