Collagen XVI Induces Expression of MMP9 via Modulation of AP-1 Transcription Factors and Facilitates Invasion of Oral Squamous Cell Carcinoma

Bedal, Konstanze B.; Grässel, Susanne; Oefner, Peter J.; Reinders, Jörg; Reichert, Torsten E.; Bauer, Robert

doi:10.1371/journal.pone.0086777

Cited by 34 publications

(28 citation statements)

References 44 publications

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“…Prior to transduction, the hTIM-4-expresssing HEK 293 stable cell line was incubated at 37°C for 30 min with increasing concentrations of arginyl-glycylaspartic acid (RGD) peptide (Abbiotec) or 3.47 inhibitor (a kind gift from Kartik Chandran, Albert Einstein College of Medicine). Concentrations were based on amounts that have been previously demonstrated to inhibit integrin binding (RGD peptide) or EBOV entry (3.47) (38)(39)(40). Cells in the presence of the inhibitor were transduced with FL EBOV VSV-GFP pseudovirions (MOI of 0.7 [titer determined on Vero cells]).…”

Section: Methodsmentioning

confidence: 99%

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry

Rhein

Brouillette

Schaack

et al. 2016

J Virol

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Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion-TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/ VSV⌬G), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions. IMPORTANCEWith more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many enveloped viruses, including EBOV. TIM family member TIM-4 is expressed on macrophages and dendritic cells, which are early cellular targets during EBOV infection. Here, we performed a mutagenesis screening of the IgV domain of murine and human TIM-4 to identify residues that are critical for EBOV entry. Surprisingly, we identified more human than murine TIM-4 IgV domain residues that are required for EBOV entry. Defining the TIM IgV residues needed for EBOV entry clarifies the virus-receptor interactions and paves the way for the development of novel therapeutics targeting virus binding to this cell surface receptor. Ebolavirus and Marburgvirus, members of the Filoviridae family, are enveloped, negative-sense RNA viruses that cause severe hemorrhagic fever in humans and nonhuman primates. A member of the Ebolavirus genus, Ebola virus (EBOV), is a causative agent of episodic filovirus outbreaks in Africa, including the most recent and deadly West African epidemic that began in December 2013 (1, 2). Contributing to the virulent nature of this virus is the ...

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Section: Methodsmentioning

confidence: 99%

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry

Rhein

Brouillette

Schaack

et al. 2016

J Virol

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“…50 AP1 has been reported to increase the transcription of MMP9, 69,70 while EGFR and integrins enhance MMP9 activity. [71][72][73][74][75] Furthermore, MMP9 degrades type IV collagen and promotes HNSCC invasion.…”

Section: Mmps In Hnscc Invasionmentioning

confidence: 98%

Matrix metalloproteinases in head and neck cancer: current perspectives

Gkouveris¹,

Nikitakis²,

Aseervatham³

et al. 2017

MNM

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Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases encoded by 24 distinct genes. Their functions have been implicated in numerous normal and pathologic processes, including uterine involution and organogenesis, inflammation and wound healing, vascular and autoimmune disease progression. Pertinent to this review, the role of MMPs in cancer biology is fairly well researched and documented, and remains a subject of continuing intense investigation. Not only are several MMPs overexpressed in head and neck squamous cell carcinomas (HNSCCs), expression has been correlated with salient tumorigenic hallmarks, such as cell proliferation, angiogenesis, invasion, and metastasis. The utility of changes in the expression profile, as well as various MMP polymorphisms as potential prognostic markers in oral cancers and oral premalignant lesions, have been investigated. Furthermore, the potential therapeutic utility of targeting MMPs in cancer remains attractive, although outcomes in this respect appear so far to be less encouraging with respect to HNSCCs. Because of the disappointing results observed in clinical trials where MMP-targeting regimens for HNSCCs utilized broad-spectrum small MMP catalytic site inhibitors, investigators now envision new strategies for MMP-specific targeting based on the recognition of new noncatalytic MMP domains with distinct functions. This review provides an overview of MMP activities in general and in cancers, and an update of their activities in HNSCC. Specifically, their role in the development and progression of HNSCC and their function as signaling molecules is discussed. Finally, their role as potential prognostic biomarkers and therapeutic targets in HNSCC is revisited.

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“…3B). It has been reported that MMP9 is associated with cell proliferation and invasion in cancers [35][36][37]. To explore whether MMP9 is associated with CCL5/CCR5-Akt pathway, the expression of MMP9 was also assessed by western blot analysis.…”

Section: Involvement Of P-akt In Ccr5-mediated Proliferation and Invamentioning

confidence: 99%

Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion

Zhao¹,

Wang²,

Xue³

et al. 2015

ABBS

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Glioblastoma (GBM) is the most prevalent malignant primary brain tumor in adults and exhibits a spectrum of aberrantly aggressive phenotype. Tumor cell proliferation and invasion are critically regulated by chemokines and their receptors. Recent studies have shown that the chemokine CCL5 and its receptor CCR5 play important roles in tumor invasion and metastasis. Nonetheless, the roles of the CCR5 in GBM still remain unclear. The present study provides the evidence that the chemokine receptor CCR5 is highly expressed and associated with poor prognosis in human GBM. Mechanistically, CCL5-CCR5 mediates activation of Akt, and subsequently induces proliferation and invasive responses in U87 and U251 cells. Moreover, down-regulation of CCR5 significantly inhibited the growth of glioma in U87 tumor xenograft mouse model. Finally, high CCR5 expression in GBM is correlated with increased p-Akt expression in patient samples. Together, these findings suggest that the CCR5 is a critical molecular event associated with gliomagenesis.

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Collagen XVI Induces Expression of MMP9 via Modulation of AP-1 Transcription Factors and Facilitates Invasion of Oral Squamous Cell Carcinoma

Cited by 34 publications

References 44 publications

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry

Matrix metalloproteinases in head and neck cancer: current perspectives

Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion

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