HGF induces EMT in non-small-cell lung cancer through the hBVR pathway

Liu, Fang; Song, Shasha; Yi, Zhi; Zhang, Min; Li, Jiali; Yang, Fang; Yin, Hongtao; Yu, Xuezhong; Chen, Guan; Liu, Ying; Liu, Zizhen; Wang, Jing; Zhu, Daling

doi:10.1016/j.ejphar.2017.05.040

Cited by 40 publications

(41 citation statements)

References 31 publications

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“…It was found that FOXP3 decreased the level of E-cadherin and increased the level of N-cadherin to stimulate EMT, resulting in enhancing tumor growth, metastasis and decrease in overall survival. In another study, Liu et al examined the effect of hepatocyte growth factor (HGF) on EMT in NSCLC (15). It was shown that HGF stimulated EMT in NSCLC cell liners A549 and H460 to enhance the cellular migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…It was found that positive expression of ZEB1 is associated with a negative E-cadherin expression, EMT induction and metastasis. Ang et al indicated the relationship between expression of ZEB family and invasiveness of breast cancer (15). In the study, it was found that upregulated microRNA-138-5p exerted inhibitory ef-fect on ZEB2 to prevent proliferation, metastasis and EMT of lung adenocarcinoma cells (16).…”

Section: Introductionmentioning

confidence: 98%

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ZEB1 and ZEB2 gene editing mediated by CRISPR/Cas9 in A549 cell line

Mohammadinejad¹,

Sassan²,

Pardakhty³

et al. 2020

BLL

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OBJECTIVES: One of the best approaches for recognition of protein function is the induction of mutations for a gene knockout. In line with this strategy, gene editing tools allow researchers to induce these mutations. Lung cancer is one of the leading causes of death worldwide. ZEB1 and ZEB2 genes are the candidates for this disease. METHODS: The ZEB1 and ZEB2 knockout in the non-small cell lung cancer cell line (A549 cell) was investigated. Purifi cation of recombination plasmids was performed from bacteria and then was transported to the A549 cell line. The deletion of ZEB1 and ZEB2 were examined by PCR. RESULTS: The results demonstrated the mutation and deletion in ZEB1 and ZEB2 genes. Based on the fi ndings of this study, A549 cells were transfected with the vectors carrying the sgRNA/Cas9, simultaneously. The DNA fragment demonstrated the presence of indels in target sites as well as provided the potential of CRISPR/Cas9 system. CONCLUSION: CRISPR/Cas9 offers a great potential as an effi cient technique for editing of ZEB1 and ZEB2 genes in A549 cell line (Tab. 1, Fig. 6, Ref.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

ZEB1 and ZEB2 gene editing mediated by CRISPR/Cas9 in A549 cell line

Mohammadinejad¹,

Sassan²,

Pardakhty³

et al. 2020

BLL

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“…These results were consistent with those of BLVRA knockdown studies in other malignancies. 7,10 Apoptosis, a conserved mechanism of programmed cell death, is malfunctioning in several cancers. Emerging evidence has shown that defective apoptosis not only promoted tumorigenesis but also brings about resistance of cancer cells to treatment.…”

Section: Discussionmentioning

confidence: 99%

“…This multitude of activities allows it to influence thousands of genes, including genes involved in signaling pathways and apoptosis, as well as cyclins. [5][6][7][8] Overexpression of BLVRA has been reported in many diseases, including cancers. The level of BLVRA is rather high in many cancers, including liver cancer, 6,9 lung cancer, 7 breast cancer, 10 skin cancer, 11 and esophageal cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>Biliverdin Reductase A (BLVRA) Promotes Colorectal Cancer Cell Progression by Activating the Wnt/β-Catenin Signaling Pathway</p>

Mao¹,

Xu²,

Zhang³

et al. 2020

CMAR

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Purpose: Biliverdin reductase A (BLVRA) is a pleiotropic enzyme that converts biliverdin-IX-alpha into the antioxidant and anti-nitrosative compound, bilirubin-IX-alpha. It is related to various diseases, including cancer. It is overexpressed in many types of cancers and promotes cancer development and metastasis, but the effects of BLVRA in colorectal cancer have not been researched at present. This study was aimed to investigate the effects of biliverdin reductase A (BLVRA) in vivo and vitro experiments and its possible mechanism. Methods: The clinical samples of CRC patients and CRC cell lines HT-29 and SW620 were chosen to perform the experiments. ELISA and Immunohistochemistry (IHC) were applied to test the level of BLVRA in patients. HT-29 knockdown of BLVRA and SW620 overexpression of BLVRA was established by the lentiviral vector transfection. Reverse transcription-quantitative real-time polymerase chain reaction and Western blotting were performed to examine the expression of BLVRA. MTT was used to detect the proliferation of CRC cells. Flow cytometry was applied to assess the rate of apoptosis. Transwell assay was performed to examine the capacity of migration and invasion. Immunofluorescence staining was adopted to assess the expression of E-cadherin and vimentin. Western blotting was utilized to detect the expression of apoptosis-related proteins, EMT-related proteins and target proteins of Wnt/β-catenin signaling pathway. Results: Analysis of the clinical samples revealed that BLVRA was overexpressed in CRC patients and implied poor prognosis. BLVRA overexpression in the in vitro studies revealed that it increased the potential of CRC cells for proliferation, migration and invasion; augmented EMT; and hindered apoptosis. In addition, BLVRA overexpression was found to upregulate positive target genes and downregulate negative target genes of the Wnt/β-catenin signaling pathway, which implied that the biological effects of BLVRA in CRC were mediated by this pathway. In contrast, knockdown of BLVRA manifested the opposite effects. Conclusion: Our results suggested that BLVRA might be a promising prognostic marker and a potential therapeutic target in CRC.

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“…Since PAS plays a critical role in hepatocyte growth factor (HGF) activation 48 that promotes the EMT of NSCLC, 49 we examined if HGF/c-Met signalling was involved in HAI-2-mediated MET of NSCLC. The data of the in vitro assay showed that active plasmin was able to proteolytically cleave pro-HGF (indicated by a release of the α-chain of HGF), and recombinant HAI-2 (rHAI-2) proteins ably inhibited plasmin function for the proteolytic cleavage of pro-HGF to HGF (Fig.…”

Section: Hai-2 Inhibits An Emt-like Transition Of Nsclc Through Supprmentioning

confidence: 99%

HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis

Lin

Shih

et al. 2019

Br J Cancer

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BACKGROUND: Dysregulation of pericellular proteolysis usually accounts for cancer cell invasion and metastasis. Isolation of a cellsurface protease system for lung cancer metastasis is an important issue for mechanistic studies and therapeutic target identification. METHODS: Immunohistochemistry of a tissue array (n = 64) and TCGA database (n = 255) were employed to assess the correlation between serine protease inhibitors (SPIs) and lung adenocarcinoma progression. The role of SPI in cell motility was examined using transwell assays. Pulldown and LC/MS/MS were performed to identify the SPI-modulated novel protease(s). A xenografted mouse model was harnessed to demonstrate the role of the SPI in lung cancer metastasis. RESULTS: Hepatocyte growth factor activator inhibitor-2 (HAI-2) was identified to be downregulated following lung cancer progression, which was related to poor survival and tumour invasion. We further isolated a serum-derived serine protease, plasmin, to be a novel target of HAI-2. Downregulation of HAI-2 promotes cell surface plasmin activity, EMT, and cell motility. HAI-2 can suppress plasmin-mediated activations of HGF and TGF-β1, EMT and cell invasion. In addition, downregulated HAI-2 increased metastasis of lung adenocarcinoma via upregulating plasmin activity. CONCLUSION: HAI-2 functions as a novel inhibitor of plasmin to suppress lung cancer cell motility, EMT and metastasis.

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HGF induces EMT in non-small-cell lung cancer through the hBVR pathway

Cited by 40 publications

References 31 publications

ZEB1 and ZEB2 gene editing mediated by CRISPR/Cas9 in A549 cell line

ZEB1 and ZEB2 gene editing mediated by CRISPR/Cas9 in A549 cell line

<p>Biliverdin Reductase A (BLVRA) Promotes Colorectal Cancer Cell Progression by Activating the Wnt/β-Catenin Signaling Pathway</p>

HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis

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