Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway

Yoshimoto, T.; Takino, Takahisa; Li, Zi‐Chen; Domoto, Takahiro; Sato, Hiroshi

doi:10.1016/j.bbrc.2014.10.154

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…These ECM proteins, among other proteins, are potential chemotherapeutic targets. Several of these ECM proteins have been associated with survival pathways such as the MEK-ERK and Akt [ 79 , 123 , 124 , 125 , 126 ]. We have to appreciate that tumors are real ecosystems harbouring several cell types and non-cellular components such as the ECM.…”

Section: Discussionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Senthebane

Jonker

Rowe

et al. 2018

IJMS

108

176

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Background: The functional interplay between tumor cells and their adjacent stroma has been suggested to play crucial roles in the initiation and progression of tumors and the effectiveness of chemotherapy. The extracellular matrix (ECM), a complex network of extracellular proteins, provides both physical and chemicals cues necessary for cell proliferation, survival, and migration. Understanding how ECM composition and biomechanical properties affect cancer progression and response to chemotherapeutic drugs is vital to the development of targeted treatments. Methods: 3D cell-derived-ECMs and esophageal cancer cell lines were used as a model to investigate the effect of ECM proteins on esophageal cancer cell lines response to chemotherapeutics. Immunohistochemical and qRT-PCR evaluation of ECM proteins and integrin gene expression was done on clinical esophageal squamous cell carcinoma biopsies. Esophageal cancer cell lines (WHCO1, WHCO5, WHCO6, KYSE180, KYSE 450 and KYSE 520) were cultured on decellularised ECMs (fibroblasts-derived ECM; cancer cell-derived ECM; combinatorial-ECM) and treated with 0.1% Dimethyl sulfoxide (DMSO), 4.2 µM cisplatin, 3.5 µM 5-fluorouracil and 2.5 µM epirubicin for 24 h. Cell proliferation, cell cycle progression, colony formation, apoptosis, migration and activation of signaling pathways were used as our study endpoints. Results: The expression of collagens, fibronectin and laminins was significantly increased in esophageal squamous cell carcinomas (ESCC) tumor samples compared to the corresponding normal tissue. Decellularised ECMs abrogated the effect of drugs on cancer cell cycling, proliferation and reduced drug induced apoptosis by 20–60% that of those plated on plastic. The mitogen-activated protein kinase-extracellular signal-regulated kinase (MEK-ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) signaling pathways were upregulated in the presence of the ECMs. Furthermore, our data show that concomitant addition of chemotherapeutic drugs and the use of collagen- and fibronectin-deficient ECMs through siRNA inhibition synergistically increased cancer cell sensitivity to drugs by 30–50%, and reduced colony formation and cancer cell migration. Conclusion: Our study shows that ECM proteins play a key role in the response of cancer cells to chemotherapy and suggest that targeting ECM proteins can be an effective therapeutic strategy against chemoresistant tumors.

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Section: Discussionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Senthebane

Jonker

Rowe

et al. 2018

IJMS

108

176

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“…Therefore, they are also considered as potential biomarkers or promising targets in the treatment of OSCC. [40][41][42]…”

Section: Disruption Of Intercellular Junctionsmentioning

confidence: 99%

“…Other molecules associated with the adherens junction in OSCC, including α‐catulin, vinculin and claudin have an impact on OSCC tumorigenesis probably by enhancing cell cycle progression, cell mobility and EMT. Therefore, they are also considered as potential biomarkers or promising targets in the treatment of OSCC 40‐42 …”

Section: Disruption Of Intercellular Junctionsmentioning

confidence: 99%

Epithelial‐to‐mesenchymal transition in oral squamous cell carcinoma: Challenges and opportunities

Ling

Cheng

Tao

2020

Intl Journal of Cancer

119

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Oral squamous cell carcinoma (OSCC) is the most common malignancy representing 90% of all forms of oral cancer worldwide. Although great efforts have been made in the past decades, the 5‐year survival rate of OSCC patients is no more than 60% due to tumor metastasis and subsequent recurrence. The metastasis from the primary site is due to a complex process known as epithelial‐to‐mesenchymal transition (EMT). During the EMT, epithelial cells gradually acquire the structural and functional characteristics of mesenchymal cells, leading to the upregulation of cell migration and the promotion of tumor cell dissemination. Therefore, EMT attracted broad attention due to its close relationship with cancer invasion and metastasis. Therefore, in the present review, an extensive description of the current research on OSCC and the role of EMT in this cancer type is provided, including diverse EMT markers, regulatory networks and crucial EMT‐inducing transcription factors in OSCC. Moreover, a brief summary was made regarding the current application of EMT‐correlated indexes in the prognostic analysis of OSCC patients, and the potential therapeutic approaches against OSCC and difficulties in the development of an effective anti‐EMT treatment are discussed. Our aim is to provide novel insights to develop new strategies to combat OSCC by targeting EMT.

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“…In melanoma cells, CD81 has been found to induce phosphorylation of Sp1, triggering MT1-MMP transcription [47]. In squamous carcinoma cells, vinculin enhances MT1-MMP production at the transcriptional level, thus increasing tumor cell invasion [48]. The binding site for Sp1, located at −125 bp upstream the translation start site, has been reported to co-operate with hypoxia-inducible factor 2α (HIF-2α) to promote MT1-MMP transcription in von Hippel–Lindau renal carcinoma cells [49,50].…”

Section: Properties Of Mt1-mmpmentioning

confidence: 99%

MT1-MMP-dependent cell migration: proteolytic and non-proteolytic mechanisms

Gifford

Itoh

2019

Biochemical Society Transactions

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Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a type I transmembrane proteinase that belongs to the matrix metalloproteinase (MMP) family. It is a potent modifier of cellular microenvironment and promotes cell migration and invasion of a wide variety of cell types both in physiological and pathological conditions. It promotes cell migration by degrading extracellular matrix on the cell surface and creates a migration path, by modifying cell adhesion property by shedding cell adhesion molecules to increase cell motility, and by altering cellular metabolism. Thus, MT1-MMP is a multifunctional cell motility enhancer. In this review, we will discuss the current understanding of the proteolytic and non-proteolytic mechanism of MT1-MMP-dependent cell migration.

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Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway

Cited by 6 publications

References 23 publications

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Epithelial‐to‐mesenchymal transition in oral squamous cell carcinoma: Challenges and opportunities

MT1-MMP-dependent cell migration: proteolytic and non-proteolytic mechanisms

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