SNX-2112 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Non-Small Cell Lung Cancer by Downregulating Epithelial-Mesenchymal Transition via the Wnt/β-Catenin Signaling Pathway

Cheng, Xinsheng; Qin, Lijie; Deng, Lian; Zhu, Xiongjie; Li, Ying; Wu, Xiaogang; Zheng, Yanfang

doi:10.7150/jca.56640

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…Studies have shown that the expression of p ‐GSK3β (SER9) is downregulated when the WNT pathway is closed, and that the downregulation of β‐catenin is a concomitant relationship rather than a causal relationship 33 . In the present study, 30,31,32,34,35,36 we found that p ‐GSK3β (SER389) is elevated when the WNT pathway is turned off, which is paradoxical with previous studies. In previous studies, it is generally believed that p ‐GSK3β (SER389), like p ‐GSK3β (SER9), is decreased when the WNT pathway is closed, whereas GSK3β (TYR216) 27 is increased, promoting the phosphorylation of β‐catenin and the final ubiquitination degradation.…”

Section: Discussioncontrasting

confidence: 99%

“…Studies have shown that the expression of p-GSK3β (SER9) is downregulated when the WNT pathway is closed, and that the downregulation of β-catenin is a concomitant relationship rather than a causal relationship. 33 In the present study, 30,31,32,34,35,36 we found that p-GSK3β (SER389) is elevated when the WNT pathway is turned off, which is paradoxical…”

Section: Discussionmentioning

confidence: 47%

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LRFN2 binding to NMDAR inhibits the progress of ESCC via regulating the Wnt/β‐Catenin and NF‐κB signaling pathway

Zhou

Wang

et al. 2022

Cancer Science

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As a neuronal transmembrane protein, leucine‐rich repeat and fibronectin type‐III domain‐containing protein 2 (LRFN2) can recruit and combine with N‐methyl‐d‐aspartate receptors (NMDARs) to promote nerve growth. Genetic studies suggest that mutations in LRFN2 are associated with various cancers. However, the role and mechanism of LRFN2 in the progression of ESCC have not been elucidated. In this study, we demonstrated that LRFN2 was significantly downregulated in ESCC tissues by qRT‐PCR and immunohistochemistry. Low LRFN2 expression was an adverse prognostic factor in patients with ESCC. Overexpression of LRFN2 effectively suppressed the proliferation, migration, invasion, and epithelial‐to‐mesenchymal transition in vitro and tumor growth in vivo. Bioinformatics analysis indicated that Wnt/β‐catenin signaling regulation was one of the most potential mechanisms and studies confirmed that overexpression of LFRN2 obviously downregulated the expression of β‐catenin, c‐Myc, and cyclin D1 in ESCC cells and tumor tissues. Further studies revealed that LRFN2 plays an anti‐ESCC role by binding with NMDAR‐GRIN2B and this effect can be weakened by NR2B‐selective NMDA antagonist‐NMDA‐IN‐1. Moreover, the bioinformatics analysis showed that the interaction of GRIN2B and GSK3β affects the NF‐κB pathway, which was demonstrated by western blot experiments. Collectively, our results indicate that LRFN2 binding to NMDARs inhibits the progression of ESCC by regulating the Wnt/β‐catenin and NF‐κB pathway, which provides a new therapeutic target for improving the prognosis of patients with ESCC.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 47%

LRFN2 binding to NMDAR inhibits the progress of ESCC via regulating the Wnt/β‐Catenin and NF‐κB signaling pathway

Zhou

Wang

et al. 2022

Cancer Science

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“…A variety of human malignancies have been linked to dysregulation of the Wnt/β-catenin signaling pathway 22 – 24 . Inhibition of the Wnt signaling pathway can suppress NSCLC cell proliferation and xenograft growth, diminish cell migration and invasion, and generate a more differentiated phenotype, all of which are essential in NSCLC 25 – 28 . CTNNB1 accumulates in the nuclei of tumor cells when the Wnt signaling pathway is activated, resulting in the loss of epithelial integrity and increased tumor invasion and metastasis 29 , 30 .…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis

Xu,

Zheng,

2024

Sci Rep

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We previously reported that circIGF1R is significantly downregulated in non-small cell lung cancer (NSCLC) cells and tissues. It inhibits cancer cell invasion and migration, although the underlying molecular mechanisms remain elusive. The invasion and migration of NSCLC cells was analyzed by routine in vivo and in vitro functional assays. Fluorescent in situ hybridization, luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation (RIP) assay were performed to explore the molecular mechanisms. Mechanism of action of paclitaxel-induced RBFOX3-mediated inhibition of NSCLC invasion and migration was investigated through in vitro and in vivo experiments.Our study reveals that circIGF1R acts as a Competing Endogenous RNA (ceRNA) for miR-1270, thereby regulating Van-Gogh-like 2 (VANGL2) expression and subsequently inhibiting NSCLC cell invasion and migration via the Wnt pathway. We also found that RNA binding protein fox-1 homolog 3 (RBFOX3) enhances circIGF1R biogenesis by binding to IGF1R pre-mRNA, which in turn suppresses migration and invasion in NSCLC cells. Additionally, the chemotherapeutic drug paclitaxel was shown to impede NSCLC invasion and migration by inducing RBFOX3-mediated circIGF1R biogenesis.RBFOX3 inhibits the invasion and migration of NSCLC cells through the circIGF1R/ miR-1270/VANGL2 axis, circIGF1R has the potential to serve as a biomarker and therapeutic target for NSCLC.

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“…Furthermore, overexpressing of β-catenin was able to rescuse the effect of FERMT2 on CRC cells. As reported that Wnt/β-catenin signaling pathway is one of the common upstream signals of EMT, and activation of this signaling pathway often induces EMT of cells in cancer [ 53 , 54 ]. FERMT2 may induce the expression of cyclin D1 and EMT related proteins by regulating the Wnt /β-catenin signaling pathway and promote the migration and invasion of CRC cells.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s risk factor FERMT2 promotes the progression of colorectal carcinoma via Wnt/β-catenin signaling pathway and contributes to the negative correlation between Alzheimer and cancer

et al. 2022

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Increasing evidence from epidemiological studies indicate that Alzheimer’s disease (AD) has a negative relationship with the incidence of cancers. Whether the Alzheimer’s genetic risk factor, named as fermitin family homolog-2 (FERMT2), plays a pivotal part in the progressive process of colorectal carcinoma (CRC) yet remains unclear. This study revealed that FERMT2 was upregulated in CRC tissues which predicted an unfavorable outcome of CRC using the PrognoScan web tool. FERMT2 was co-expressed with a variety of genes have been linked with CRC occurrence and implicated in the infiltration of immune cell in CRC tissues. Overexpressing FERMT2 promoted CRC progression with upregulation of Wnt/β-catenin signaling. Knockdown of FERMT2 suppressed the cell multiplication, colony formation rate, migration and invasion, along with the epithelial to mesenchymal transition (EMT) with downregulation Wnt/β-catenin proteins in cells of CRC, while overexpressing β-catenin reversed the inhibitory effects of silencing FERMT2 on the migration or invasion of CRC cells. Furthermore, Aβ1–42 treated HT22 cells induced downregulation of FERMT2 and inhibited the migration, invasion and EMT in co-cultured CT26 cells through Wnt/β-catenin signaling. Our results revealed that the downregulated FERMT2 gene during AD is prominently activated in CRC, which promotes its progression via Wnt/β-catenin pathway.

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SNX-2112 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Non-Small Cell Lung Cancer by Downregulating Epithelial-Mesenchymal Transition via the Wnt/β-Catenin Signaling Pathway

Cited by 9 publications

References 42 publications

LRFN2 binding to NMDAR inhibits the progress of ESCC via regulating the Wnt/β‐Catenin and NF‐κB signaling pathway

LRFN2 binding to NMDAR inhibits the progress of ESCC via regulating the Wnt/β‐Catenin and NF‐κB signaling pathway

Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis

Alzheimer’s risk factor FERMT2 promotes the progression of colorectal carcinoma via Wnt/β-catenin signaling pathway and contributes to the negative correlation between Alzheimer and cancer

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