LRG1 modulates invasion and migration of glioma cell lines through TGF-β signaling pathway

Zhong, Di; He, Guangxu; Zhao, Siren; Li, Jinku; Lang, Yanbin; Ye, Wei; Li, Yongli; Jiang, Chuanlu; Li, Xianfeng

doi:10.1016/j.acthis.2015.05.001

Cited by 39 publications

(43 citation statements)

References 42 publications

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“…Consistently, LRG1 promotes angiogenesis by modulating endothelial TGF-β signaling in retinal vascular [5] and NSCLC [22]. LRG1 can also modulate the invasion and migration of glioma cell lines through the TGF-β signaling pathway [23]. Thus, we hypothesized that LRG1 promotes ccRCC progression via the TGF-β pathway based on this evidence.…”

Section: Discussionmentioning

confidence: 77%

LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

Hong

Wang

Liu

et al. 2020

BioMed Research International

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Clear cell renal cell carcinoma (ccRCC) accounts for 60-70% of renal cell carcinoma (RCC) cases. It is an urgent mission to find more therapeutic targets for advanced ccRCC. Leucine-rich a-2-glycoprotein 1 (LRG1) is a secreted protein associated with a variety of malignancies. Our study focused on the expression and mechanism of LRG1 in ccRCC based on data from The Cancer Genome Atlas (TCGA) and provided primary verification including LRG1 expression detection, LRG1 gene methylation detection, and downstream signaling detection. We found that LRG1 was overexpressed in ccRCC kidney tissue samples, and the methylation level of LRG1 gene was significantly decreased in ccRCC. Moreover, the expression of LRG1 was negatively related to patient survival. Based on our previous study and the verification reported in this article, we propose that demethylation-induced overexpression of LRG1 is likely to accelerate ccRCC progression via the TGF-β pathway.

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Section: Discussionmentioning

confidence: 77%

LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

Hong

Wang

Liu

et al. 2020

BioMed Research International

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“…LRG1 has been reported to be highly expressed in gastric cancer, colorectal cancer, brain glioma and other tumors [17,32,33]. The high expression of LRG1 was found to promote the invasion and migration of those cancer cells.…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2020

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Background: 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. 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 TGFβ 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 TGFβ signaling and EMT of ESCC cells. Conclusion/Significance: LRG1 suppresses ESCC cell migration and invasion via negative modulation of TGFβ signaling and EMT. Down-regulation of LRG1 in ESCC patients may favor tumor metastasis and disease progression.

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“…Recent studies showed that LRG1 promotes pathogenic neovascularization, cell adhesion, cell migration, and cell invasion and is involved in the epithelial-to-mesenchymal transition (EMT) process[10, 26, 27]. As proliferation play an important role in the carcinogenesis of tumours, and the cell cycle of eukaryotic cells is the essential process of cell proliferation[28], we investigated the role of LRG1 in the proliferation and the cell cycle of CRC cells.…”

Section: Discussionmentioning

confidence: 99%

LRG1 promotes proliferation and inhibits apoptosis in colorectal cancer cells via RUNX1 activation

Zhou

Zhang

et al. 2017

PLoS ONE

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Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has been shown to be involved in various human malignancies. Whether it plays a role in colorectal cancer (CRC) development remains unclear. Here, we investigated whether and through what mechanism LRG1 functions in human CRC cells. The plasma level of LRG1 was significantly increased in CRC patients, but it was remarkably decreased in patients with resected colorectal cancers. Meanwhile, both mRNA and protein levels of LRG1 were remarkable overexpressed in CRC tissues than normal tissues. The knockdown of LRG1 significantly inhibited cell proliferation, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis in SW480 and HCT116 cells in vitro. In addition, LRG1 silencing led to the downregulation of the levels of key cell cycle factors, such as cyclin D1, B, and E and anti-apoptotic B-cell lymphoma-2(Bcl-2). However, it up-regulated the expression of pro-apoptotic Bax and cleaved caspase-3. Furthermore, RUNX1 could be induced by LRG1 in a concentration-dependent manner, while the knockdown of RUNX1 blocked the promotion of the proliferation and inhibition of apoptosis induced by LRG1. Collectively, these findings indicate that LRG1 plays a crucial role in the proliferation and apoptosis of CRC by regulating RUNX1 expression. Thus, LRG1 may be a potential detection biomarker as well as a marker for monitoring recurrence and therapeutic target for CRC.

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LRG1 modulates invasion and migration of glioma cell lines through TGF-β signaling pathway

Cited by 39 publications

References 42 publications

LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

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

LRG1 promotes proliferation and inhibits apoptosis in colorectal cancer cells via RUNX1 activation

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