Dataset Information

LRG1 Suppresses Migration and Invasion of Esophageal Squamous Cell Carcinoma by Modulating Epithelial to Mesenchymal Transition.

ABSTRACT: Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. The molecular pathogenesis underlying ESCC remains to be explored. Leucine-rich ?-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of various cancer types, however its role in ESCC is unknown. Materials and Methods: Data from the public database was analyzed to address the expression of LRG1 in ESCC. Gain-of-function studies were performed in select ESCC cell lines by over-expression or addition of recombinant LRG1, while loss-of-function studies achieved by small interfering RNA mediated knockdown. Wound healing and transwell assays were conducted to investigate ESCC cell migration and invasion upon manipulating LRG1 levels. Western blot and Immunofluorescence staining were used to examine the changes in epithelial to mesenchymal transition (EMT) and TGF? signaling pathway. Results: LRG1 mRNA levels were found to be significantly down-regulated in patients with ESCC as well as in several ESCC cell lines. Silencing of LRG1 promoted, while overexpression of LRG1 inhibited ESCC cell migration and invasion. In line with this, Silencing of LRG1 enhanced, while overexpression of LRG1 reduced TGF? signaling and EMT of ESCC cells. Conclusion/Significance: LRG1 suppresses ESCC cell migration and invasion via negative modulation of TGF? signaling and EMT. Down-regulation of LRG1 in ESCC patients may favor tumor metastasis and disease progression.

SUBMITTER: Zhang N

PROVIDER: S-EPMC6995366 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LRG1 Suppresses Migration and Invasion of Esophageal Squamous Cell Carcinoma by Modulating Epithelial to Mesenchymal Transition.

Zhang Ninggang N Ren Yaqiong Y Wang Yusheng Y Zhao Lei L Wang Bin B Ma Nina N Gao Zhengxing Z Cao Bangwei B

Journal of Cancer 20200114 6

<b>Background</b>: Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. The molecular pathogenesis underlying ESCC remains to be explored. Leucine-rich ɑ-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of various cancer types, however its role in ESCC is unknown. <b>Materials and Methods</b>: Data from the public database was analyzed to address the expression of LRG1 in ESCC. Gain-of-function studies were performed in select ESCC cell lines by over-e ...[more]

PMID: 32047555

Similar Datasets

Project description:ObjectiveInhibition of tumor metastasis is a useful strategy to improve the efficacy of cancer therapy. Ventilagolin, a natural 1, 4-naphthoquinone derivative extracted from Ventilago leiocarpa Benth, has shown promising antitumor effects in previous studies. However, the effects and underlying mechanisms of Ventilagolin against migration, invasion and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) remain unclear. The present study has examined these effects and determined whether the proto-oncogene Pim-1 is involved.MethodsThe effects of Ventilagolin on migration, invasion, Pim-1 and EMT-related proteins (eg, E-cadherin, N-cadherin, Vimentin) expression were assessed by scratch wound healing, Transwell, qRT-PCR and Western blot assays, respectively. Pim-1 stably overexpressed HepG2 and SMMC-7721 cells were generated to explore whether Ventilagolin inhibited migration, invasion and EMT of HCC cells via regulating Pim-1. Subcutaneous xenograft tumor model in nude mice was established. Histopathological changes of tumor tissues were examined by H&E staining and expressions of Pim-1 and EMT-related proteins were detected by immunohistochemistry.ResultsVentilagolin significantly (P < 0.01) reduced the expression of Pim-1 levels in HepG2 and SMMC-7721 cells. Compared with the control group, the migration and invasion abilities of Pim-1-overexpressing HepG2 and SMMC-7721 cells were significantly (P < 0.05, P < 0.01) enhanced, the expression of E-cadherin was decreased (P < 0.01), and the levels of N-cadherin and Vimentin were upregulated (P < 0.05, P < 0.01). Ventilagolin treatment effectively reversed these effects of Pim-1 overexpression. In vivo experiments showed that Ventilagolin could effectively suppress HCC tumor growth, downregulate Pim-1, N-cadherin and Vimentin expression, and upregulate E-cadherin expression.ConclusionVentilagolin suppresses HCC cell proliferation, migration and invasion and reverses EMT process by downregulating Pim-1, suggesting Ventilagolin is a potential therapeutic agent for treatment of HCC.

Project description:Esophageal squamous cell carcinoma (ESCC) is a malignant disease with poor prognosis. Because of early metastasis prior to diagnosis and therapeutic resistance, ESCC has become one of the leading causes of cancer-related death. Here, we investigated the clinicopathological significance of the association of octamer-binding transcription factor 4 (OCT4) with lymphoid enhancer-binding factor 1 (LEF1) expression and the potential molecular mechanism in the epithelial-mesenchymal transition (EMT), invasion, and migration of ESCC. The expression of OCT4 and LEF1 was detected via immunohistochemistry analysis. High levels of LEF1 expression were observed in 95 ESCC specimens and were obviously associated with aberrant clinicopathological features and poor patient prognosis. Our previous study showed that OCT4 expression level is elevated in ESCC, and statistical analysis showed that the elevated expression of OCT4 and LEF1 in ESCC was significantly associated with histologic grade, lymph node metastasis, TNM stage, and poor patient prognosis. The specific inhibition of OCT4 expression via a lentivirus encoding OCT4-shRNA (LV-shOCT4) in Eca109 cells led to decreased levels of OCT4 and LEF1 in vitro. Additionally, we applied a rescue strategy by infecting LV-shOCT4 Eca109 cells with a LEF1 overexpression plasmid (p-LEF1) and detected changes in EMT, migration, and invasion. Unsurprisingly, the p-LEF1 group exhibited greater EMT, invasion, and migration than did the LV-shOCT4 and negative control groups. This study demonstrates for the first time the relationship between OCT4 and LEF1 expression. The combination of high expression of OCT4 and LEF1 was associated with clinicopathological features of atypical patients, and this combination might be an ideal prognostic factor in ESCC. OCT4 positively regulated LEF1 expression, and LEF1 mediated the effects of OCT4 in cancer cell EMT, invasion, and migration. The data presented here suggest that the inhibition of OCT4-LEF1 signaling may be a new therapeutic target for the treatment of ESCC.

Dataset Information

LRG1 Suppresses Migration and Invasion of Esophageal Squamous Cell Carcinoma by Modulating Epithelial to Mesenchymal Transition.

Publications

LRG1 Suppresses Migration and Invasion of Esophageal Squamous Cell Carcinoma by Modulating Epithelial to Mesenchymal Transition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets