MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin

Fernández‐Figueras, María‐Teresa; Carrato, Cristina; Sàenz-Sardà, Xavier; Musulén, Eva; Fuente, M.J.; Puig, Lluís

doi:10.1007/s00403-021-02288-x

Cited by 4 publications

(4 citation statements)

References 88 publications

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“…Epithelial-mesenchymal transformation (EMT) has been considered a necessary regulatory mechanism for the migration and invasion of malignant tumors in recent years [ 18 ]. The latest investigations indicate that MMP1 plays a vital role in EMT in colorectal cancer and squamous cell carcinoma of the skin [ 11 , 19 ]. Nevertheless, the precise biological functions of MMP1 in HNSCC are just now beginning to surface in selected contexts and the associations between MMP1 and EMT remain yet unexplored in HNSCC.…”

Section: Introductionmentioning

confidence: 99%

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma

Zhang

Huang

et al. 2022

Computational and Mathematical Methods in Medicine

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Matrix metalloproteinase-1 (MMP1) has been reported to play key roles in a variety of cancers by degrading the extracellular matrix. However, its carcinogenic roles have not been shown yet in head and neck squamous cell carcinoma (HNSCC). This study aimed to elucidate its expression pattern and functional roles as well as clinical significance in HNSCC. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and immunohistochemistry (IHC) were utilized to determine the MMP1 expression pattern and the associations between its expression and patients’ outcome in HNSCC. Mice tongue squamous cell carcinoma model induced by 4-nitroquinoline 1-oxide (4NQO) and siRNA-mediated cellular assay in vitro were utilized to evaluate the oncogenic role of MMP1. The biological functions and cancer-related pathways involved in MMP1-related genes were found through bioinformatics analysis. Both mRNA and protein abundance of MMP1 were highly increased in HNSCC as compared to its non-tumor counterparts. MMP1 overexpression positively correlated with advanced tumor size, cervical node metastasis, and advanced pathological grade and lower patients’ survival. In the 4NQO-induced animal model, MMP1 expression increased along with the progression of the disease. In HNSCC cells, siRNA-mediated knockdown of MMP1 significantly inhibited cell proliferation, migration, and invasion and activated apoptosis and epithelia-mesenchymal transition (EMT). GSEA, GO, and KEGG analyses showed that MMP1 expression was significantly related to cancer-related pathways and cancer-related functions. Together, our results demonstrated MMP1 serves as a novel prognostic biomarker and putative oncogene in HNSCC.

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Section: Introductionmentioning

confidence: 99%

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma

Zhang

Huang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Additionally, the proliferation marker Ki67 was significantly increased in cSCC arising through the classical pathway [ 51 ]. Additional differences between the pathways include increased miR-31 and MMP levels in the differentiated pathway [ 52 ]. Nevertheless, the expression of markers at the invasive front of cSCC and Bowen’s disease acquiring de novo invasive ability suggest a pivotal role of the EMT process in facilitating invasion in cSCC [ 51 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

“…The evidence presented confirms that in cSCC the acquisition of advanced EMT features represents the point of transition from benign to malignant, non-invasive to invasive disease. A major difference between differentiated and classical pathway of cSCC progression is the aggressiveness of the arising tumors as well as the point during the progression where tumor cells displaying advanced EMT markers (Vimentin, Zeb1) can be observed [ 51 , 52 ]. During the differentiated pathway, the point of acquiring invasive capabilities coincides with the expression of advanced EMT markers.…”

Section: Discussionmentioning

confidence: 99%

A tEMTing target? Clinical and experimental evidence for epithelial-mesenchymal transition in the progression of cutaneous squamous cell carcinoma (a scoping systematic review)

et al. 2022

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Cutaneous squamous cell carcinoma (cSCC) is a disease with globally rising incidence and poor prognosis for patients with advanced or metastatic disease. Epithelial-mesenchymal transition (EMT) is a driver of metastasis in many carcinomas, and cSCC is no exception. We aimed to provide a systematic overview of the clinical and experimental evidence for EMT in cSCC, with critical appraisal of type and quality of the methodology used. We then used this information as rationale for potential drug targets against advanced and metastatic cSCC. All primary literature encompassing clinical and cell-based or xenograft experimental studies reporting on the role of EMT markers or related signalling pathways in the progression of cSCC were considered. A screen of 3443 search results yielded 86 eligible studies comprising 44 experimental studies, 22 clinical studies, and 20 studies integrating both. From the clinical studies a timeline illustrating the alteration of EMT markers and related signalling was evident based on clinical progression of the disease. The experimental studies reveal connections of EMT with a multitude of factors such as genetic disorders, cancer-associated fibroblasts, and matrix remodelling via matrix metalloproteinases and urokinase plasminogen activator. Additionally, EMT was found to be closely tied to environmental factors as well as to stemness in cSCC via NFκB and β-catenin. We conclude that the canonical EGFR, canonical TGF-βR, PI3K/AKT and NFκB signalling are the four signalling pillars that induce EMT in cSCC and could be valuable therapeutic targets. Despite the complexity, EMT markers and pathways are desirable biomarkers and drug targets for the treatment of advanced or metastatic cSCC. Graphical Abstract

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“… 2021 ; Fernandez-Figueras et al. 2022 ). In addition, miRNAs are vital modulators in the progression of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis

Wang

Zou

et al. 2023

Pharmaceutical Biology

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Context Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. Objective Our study explores the effect and mechanism of STS against LUAD. Materials and methods LUAD cells were treated with 100 μM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. Results STS significantly decreased the viability (40–50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. Discussion and Conclusions STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

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MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin

Cited by 4 publications

References 88 publications

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma

A tEMTing target? Clinical and experimental evidence for epithelial-mesenchymal transition in the progression of cutaneous squamous cell carcinoma (a scoping systematic review)

Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis

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