MFAP2 promotes epithelial&amp;ndash;mesenchymal transition in gastric cancer cells by activating TGF-&amp;beta;/SMAD2/3 signaling pathway

Wang, Jiankai; Wang, Wen‐Juan; Cai, Hao; Du, Binbin; Mai, Ping; Zhang, Lijuan; Ma, Wen; Hu, Youyou; Feng, Shi-Fang; Miao, Guoying

doi:10.2147/ott.s160831

Cited by 45 publications

(55 citation statements)

References 50 publications

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“…3c, GC cell lines expressed more MFAP2 than GES-1. We also found that a previous study had verified that MFAP2 was upregulated in GC among 168 paired samples by immunohistochemistry 24 . These findings demonstrated that MFAP2 was upregulated in GC, implying the importance of them in GC pathogenesis.…”

Section: Mfap2 Is Upregulated In Gc Tissues and Cell Linessupporting

confidence: 79%

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway

Yao

Zhang

et al. 2020

Oncogenesis

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Gastric cancer (GC) is one of the most common malignancies and its prognosis is extremely poor. This study identifies a novel oncogene, microfibrillar-associated protein 2 (MFAP2) in GC. With integrative reanalysis of transcriptomic data, we found MFAP2 as a GC prognosis-related gene. And the aberrant expression of MFAP2 was explored in GC samples. Subsequent experiments indicated that silencing and exogenous MFAP2 could affect motility of cancer cells. The inhibition of silencing MFAP2 could be rescued by another FAK activator, fibronectin. This process is probably through affecting the activation of focal adhesion process via modulating ITGB1 and ITGA5. MFAP2 regulated integrin expression through ERK1/2 activation. Silencing MFAP2 by shRNA inhibited tumorigenicity and metastasis in nude mice. We also revealed that MFAP2 is a novel target of microRNA-29, and miR-29/MFAP2/integrin α5β1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression. In conclusion, our data identified MFAP2 as a novel oncogene in GC and revealed that miR-29/MFAP2/ integrin α5β1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression.

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Section: Mfap2 Is Upregulated In Gc Tissues and Cell Linessupporting

confidence: 79%

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway

Yao

Zhang

et al. 2020

Oncogenesis

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“…MFAP2 is a component of microfibrils. 28 An in vivo assay shows that MFAP2 regulates hemostasis and thrombosis. 29 Few studies were conducted to investigate MFAP2 function in cancer.…”

Section: Discussionmentioning

confidence: 99%

lncRNA LCPAT1 Upregulation Promotes Breast Cancer Progression via Enhancing MFAP2 Transcription

Gong

Dong

Niu

et al. 2020

Molecular Therapy - Nucleic Acids

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The importance of long noncoding RNA (lncRNA) in tumorigenesis has been supported by increasing evidence in recent years. However, the mechanism linking lncRNA function with cancer progression remains poorly understood. lncRNA LCPAT1 plays a role in lung cancer. However, how it works in breast cancer (BC) is largely unclear. In this study, we found that LCPAT1 was highly expressed in BC tissues and cell lines. High LCPAT1 expression predicted a low survival rate in BC patients. LCPAT1 promoted BC cell proliferation, migration, and invasion while inhibiting apoptosis in vitro . LCPAT1 knockdown suppressed BC growth in vivo and vice versa. LCPAT1 interacted with RBBP4 and recruited it to the MFAP2 (microfibril-associated protein 2) promoter and then activated MFAP2 transcription. Restoration of MFAP2 rescued the effects of LCPAT1 knockdown in BC cells. In sum, LCPAT1 promotes BC progression through recruiting RBBP4 to initiate MFAP2 transcription.

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“…In addition, MFAP2 has been shown to be markedly elevated in head and neck squamous cell carcinoma, particularly in lymph node metastasis (34). Recently, Wang et al (35) demonstrated that MFAP2 can promote epithelial-mesenchymal transition via activating the TGF-β/SMAD2/3 signaling pathway in GC cells. Consistent with previous findings, our results suggested that MFAP2 may play a crucial role in progression of GC and that it may act as an oncogene.…”

Section: Discussionmentioning

confidence: 99%

Integrated profiling identifies SLC5A6 and MFAP2 as novel diagnostic and prognostic biomarkers in gastric cancer patients

et al. 2019

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Gastric cancer (GC) is one of the leading causes of malignancy-associated mortality worldwide. However, the underlying molecular mechanisms of GC are unclear and the prognosis of GC is poor. Therefore, it is important and urgent to explore the underlying mechanisms and screen for novel diagnostic and prognostic biomarkers, as well as therapeutic targets. In the current study, scale-free gene co-expression networks were constructed using weighted gene co-expression network analysis, the potential associations between gene sets and clinical features were investigated, and the hub genes were identified. The gene expression profiles of GSE38749 were downloaded from the Gene Expression Omnibus database. RNA-seq and clinical data for GC from The Cancer Genome Atlas were utilized for verification. Furthermore, the expression of candidate biomarkers in gastric tissues was investigated. Survival analysis was performed using Kaplan-Meier and log-rank test. The predictive role of candidate biomarkers in GC was evaluated using a receiver operator characteristic (ROC) curve. Gene Ontology, gene set enrichment analysis and gene set variation analysis methods were used to interpret the function of candidate biomarkers in GC. A total of 29 modules were identified via the average linkage hierarchical clustering. A significant module consisting of 48 genes associated with clinical traits was found; three genes with high connectivity in the clinical significant module were identified as hub genes. Among them, SLC5A6 and microfibril-associated protein 2 (MFAP2) were negatively associated with the overall survival, and their expression was elevated in GC compared with non-tumor tissues. Additionally, ROC curves indicated that SLC5A6 and MFAP2 showed a good diagnostic power in discriminating cancerous from normal tissues. SLC5A6 and MFAP2 were identified as novel diagnostic and prognostic biomarkers in GC patients; both of these genes were first reported here in connection with GC and deserved further research.

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MFAP2 promotes epithelial–mesenchymal transition in gastric cancer cells by activating TGF-β/SMAD2/3 signaling pathway

Cited by 45 publications

References 50 publications

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway

lncRNA LCPAT1 Upregulation Promotes Breast Cancer Progression via Enhancing MFAP2 Transcription

Integrated profiling identifies SLC5A6 and MFAP2 as novel diagnostic and prognostic biomarkers in gastric cancer patients

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