ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2

Cheng, Tingting; Zhang, Zijian; Cheng, Yu‐Yu; Zhang, Jing; Tang, Jianbing; Tan, Zhaohua; Liang, Zhihou; Chen, Taili; Liu, Zhiyuan; Li, Jiahui; Zhao, Jin; Zhou, Rongrong

doi:10.1016/j.bbrc.2019.06.115

Cited by 22 publications

(20 citation statements)

References 28 publications

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“…Previous studies have reported that ETV4 mRNA is frequently overexpressed in lung AC. 12,13 However, the clinical significance of ETV4 in NSCLC progression, especially in SCC, still lacks evidence.…”

Section: Discussionmentioning

confidence: 99%

“…3 ETV4 has previously been reported to play important roles in the regulation of gene expression during early embryogenesis, 4,5 oncogenesis, [6][7][8][9][10] obesity, and diabetes. 11 In NSCLCs, the ETV4 messenger RNA (mRNA) is frequently overexpressed in AC, 12,13 and ETV4-MMP24 axis was recently identified as a critical biomarker of lung AC progression. 14 Furthermore, ETV4 might serve as a substitute for EGFR signaling to drive the survival of EGFR-mutant lung ACs upon gefitinib, erlotinib, or the third-generation EGFR inhibitor AZD9291 treatment.…”

Section: Introductionmentioning

confidence: 99%

“…So far, a few ETV4 target genes involved in the regulation of malignant potential of cancer cells have been described, including the activation of genes encoding matrix metalloproteases, [7][8][9] cell cycle regulators, 17,18 or other cancerrelated factors, such as malic enzyme 1 and Tafazzin (TAZ). 19,20 While in lung cancer, its known targeted genes only include MSI2, 13 matrix metalloproteinase 24 (MMP24), 14 ROCK, 21 and 4-galactosyltransferase I (GalT-I8). 22 Therefore, identifying other undefined functional targets will provide a better understanding of the molecular mechanisms involved in ETV4-driven lung tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

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ETV4 overexpression promotes progression of non–small cell lung cancer by upregulating PXN and MMP1 transcriptionally

Wang

Ding

Liu

et al. 2019

Molecular Carcinogenesis

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ETS variant 4 (ETV4), together with ETV1 and ETV5, constitute the PEA3 subfamily of ETS transcription factors, which are implicated in the progression of many cancers.However, the clinicopathologic significance and molecular events regulated by ETV4 in lung cancer are still poorly understood, especially in squamous cell carcinoma of the lung. Here, we aimed to identify functional targets involved in ETV4-driven lung tumorigenesis. Microarray analysis and validation data revealed that ETV4 was the most preponderant PEA3 factor, which was significantly related to the advanced stage, lymph node metastasis, and poor prognosis of non-small cell lung cancers (NSCLCs; all P < .001). Reduced ETV4 expression suppressed the growth and metastasis of NSCLC both in vivo and in vitro. Microarray, gain, or loss of function and luciferase report assays revealed the direct regulatory effect of ETV4 on the expression of focal adhesion gene PXN and matrix metalloproteinase 1 (MMP1), and PXN and/or MMP1 inhibition partially abolished cell proliferation and migration induced by ETV4. Kaplan-Meier analysis indicated that ETV4 and PXN or MMP1 cooverexpression is associated with poor prognosis in human NSCLCs. In conclusion, the ETV4-PXN and ETV4-MMP1 axes are useful biomarkers of tumor progression and worse outcomes in NSCLCs. K E Y W O R D S ETV4, non-small cell lung cancer, prognosis, PXN

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

ETV4 overexpression promotes progression of non–small cell lung cancer by upregulating PXN and MMP1 transcriptionally

Wang

Ding

Liu

et al. 2019

Molecular Carcinogenesis

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“…As some examples, MSI2 expression is upregulated by RANKL, which is a receptor activator of NF-kB ligand, during osteoclast differentiation. 34 Chromatin immunoprecipitation (ChIP) and luciferase reporter assays showed that ETV4 directly binds to the promoter of MSI2 and promotes its transcription in lung adenocarcinoma, 35 while KLF4 represses MSI2 transcription by directly binding to its promoter in pancreatic cancer cells. 36 In breast cancer, DBC2 directly interacts with MSI2, to promote MSI2 polyubiquitination, suppress MSI2-associated oncogenic functions, and induce apoptosis.…”

Section: Regulation Of Musashi-2mentioning

confidence: 99%

Potential Role of Musashi-2 RNA-Binding Protein in Cancer EMT

Sun¹,

Sheng²,

Ma³

et al. 2021

OTT

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Local invasion and distant metastasis are the key hallmarks in the aggressive progression of malignant tumors, including the ability of cancer cells to detach from the extracellular matrix overcome apoptosis, and disseminate into distant sites. It is generally believed that this malignant behavior is stimulated by epithelial-mesenchymal transition (EMT). Musashi (MSI) RNA-binding proteins, belonging to the evolutionarily conserved RNA-binding proteins (RBP) family, were originally discovered to regulate asymmetric cell division during embryonic development. Recently, Musashi-2 (MSI2), as a key member of MSI family, has been prevalently reported to be tightly associated with the advanced clinical stage of several cancers. Multiple oncogenic signaling pathways mediated by MSI2 play vital roles in EMT. Here, we systematically reviewed the detailed role and signal networks of MSI2 in regulating cancer development, especially in EMT signal transduction, involving EGF, TGF-β, Notch, and Wnt pathways.

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“…For example, PYCR1 may be a novel therapeutic target for inhibiting cell proliferation in lung cancer [48]. ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2 [49]. Knockdown of PITX2 inhibits cell proliferation, migration and invasion of LUAD [50].…”

Section: Mcm2 13mentioning

confidence: 99%

Identifying critical state of complex diseases by single-sample Kullback–Leibler divergence

2020

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Background: Developing effective strategies for signaling the pre-disease state of complex diseases, a state with high susceptibility before the disease onset or deterioration, is urgently needed because such state usually followed by a catastrophic transition into a worse stage of disease. However, it is a challenging task to identify such predisease state or tipping point in clinics, where only one single sample is available and thus results in the failure of most statistic approaches. Methods: In this study, we presented a single-sample-based computational method to detect the early-warning signal of critical transition during the progression of complex diseases. Specifically, given a set of reference samples which were regarded as background, a novel index called single-sample Kullback-Leibler divergence (sKLD), was proposed to explore and quantify the disturbance on the background caused by a case sample. The pre-disease state is then signaled by the significant change of sKLD. Results: The novel algorithm was developed and applied to both numerical simulation and real datasets, including lung squamous cell carcinoma, lung adenocarcinoma, stomach adenocarcinoma, thyroid carcinoma, colon adenocarcinoma, and acute lung injury. The successful identification of pre-disease states and the corresponding dynamical network biomarkers for all six datasets validated the effectiveness and accuracy of our method. Conclusions: The proposed method effectively explores and quantifies the disturbance on the background caused by a case sample, and thus characterizes the criticality of a biological system. Our method not only identifies the critical state or tipping point at a single sample level, but also provides the sKLD-signaling markers for further practical application. It is therefore of great potential in personalized pre-disease diagnosis.

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ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2

Cited by 22 publications

References 28 publications

ETV4 overexpression promotes progression of non–small cell lung cancer by upregulating PXN and MMP1 transcriptionally

ETV4 overexpression promotes progression of non–small cell lung cancer by upregulating PXN and MMP1 transcriptionally

Potential Role of Musashi-2 RNA-Binding Protein in Cancer EMT

Identifying critical state of complex diseases by single-sample Kullback–Leibler divergence

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