GALNT2 promotes cell proliferation, migration, and invasion by activating the Notch/Hes1-PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma

Wang, Wei; Sun, Ruiying; Zeng, Lizhong; Chen, Yang; Zhang, Na; Cao, Shiguang; Deng, Shanshan; Xia, Meng; Yang, Shuanying

doi:10.1016/j.lfs.2021.119439

Cited by 20 publications

(16 citation statements)

References 26 publications

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“…KRT6A promotes lung cancer cell growth and invasion through MYC-Regulated pentose phosphate pathway (28). Furthermore, GALNT2 promotes cell proliferation, migration and invasion by activating the Notch/Hes1-PTEN-PI3K/Akt signaling pathway in LUAD (29). The above results show that LDHA, DKK1, MELTF, VDAC1, FUT4, PLK1, KRT6A and GALNT2 promotes tumor progression in LUAD suggesting its role as an oncogene.…”

Section: Discussionmentioning

confidence: 70%

Development and validation of endoplasmic reticulum stress-related eight-gene signature for predicting the overall survival of lung adenocarcinoma

Lin¹,

Zhang²

2022

Transl Cancer Res TCR

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Background: The high case-fatality rate of patients with lung adenocarcinoma (LUAD) emphasizes the importance of identifying a robust and reliable prognostic signature for LUAD patients. Endoplasmic reticulum (ER) stress results from protein misfolding imbalance and has been shown to participate in the development of cancer. We aimed to develop and validation a reliable and robust ER stress-related prognostic signature to accurately predict prognosis for patients with LUAD.Methods: The mRNA expressions data and the clinical information were downloaded from The Cancer Genome Atlas (TCGA) as training set. The data of external validation sets were downloaded from GEO database with the accession number GSE 30219, GSE 31210, GSE 50081 and GSE 37745. Univariate Cox regression analyses was performed to identify mRNAs associated with overall survival (OS) in LUAD. ERassociated genes were retrieved using GeneCards database. Next, we construct the best risk score model by the least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation.Subsequently, predictive models and risk scores were developed in the TCGA training dataset. Cox proportional hazards regression models were used for univariate and multivariate analysis of risk score and clinicopathologic characteristics. As a validation set GSE30219, GSE31210 and (GSE50081+GSE37745) were used to validate the predictive performance of the model in TCGA. Finally, functional enrichment analysis, including the gene ontology (GO) enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene set enrichment analysis (GSEA) were performed to further explore function and mechanisms.Results: A prognostic prediction model based on eight genes was developed in the TCGA training dataset.As expected, in validation sets, patients with higher risk scores were found to have worse prognosis. Timedependent ROC curve analyses demonstrated that the risk score model was reliable. The nomograms showed excellent predictive ability. Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for LUAD. Additionally, functional enrichment analysis showed that the relevant biomarkers were enriched in cell cycle and glycolysis related signaling pathways. Conclusions:The 8-gene signature may enable improved the prediction of clinical events and decisions about management of LUAD.

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Section: Discussionmentioning

confidence: 70%

Development and validation of endoplasmic reticulum stress-related eight-gene signature for predicting the overall survival of lung adenocarcinoma

Lin¹,

Zhang²

2022

Transl Cancer Res TCR

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“…The possible interactions of these proteins were analyzed using bioinformatics, and several hub proteins were identified. Among these, we have already verified the expression and function of DHX9 ( Cao et al, 2017 ; Yan et al, 2019 ), ADFP ( Meng et al, 2021 ; Zhang et al, 2014 ), and GALNT2 ( Wang et al, 2021 ) in LUAD in vitro and in vivo models, patient databases and tissue samples. In the present study, we analyzed the role of SPC21 in LUAD progression and evaluated its value as a prognostic indicator and therapeutic target.…”

Section: Introductionmentioning

confidence: 84%

Signal peptidase 21 suppresses cell proliferation, migration, and invasion via the PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma

Zhang

Cao

Sun

et al. 2022

PeerJ

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Background In a previous study, a total of 568 differentially expressed proteins including the signal peptidase SPC21 were identified from lung adenocarcinoma (LUAD) and paired normal lung tissues. In this study, the role of SPC21 in LUAD progression was investigated. Methods The relationships and protein-protein interaction network of proteins differentially expressed between paired LUAD samples and adjacent normal tissues samples were identified via the String and Pajek software, respectively. The expression levels of the hub protein SPC21 were analyzed in 84 LUAD-normal paired tissues via immunohistochemistry. The prognostic value of SPC21 mRNA was investigated in 478 LUAD patients from TCGA and GTEx datasets. siRNAs were used in A549 and NCI-H1299 cells to knockdown SPC21. The SPC21 biological function was evaluated using the CCK-8, EdU, plate colony formation, transwell, wound healing, and adhesion assays. Results Patients with lower SPC21 mRNA levels tended to have worse prognosis (overall survival) than those with higher mRNA levels. SPC21 expression was significantly downregulated in LUAD tumor tissues compared with that in paired normal tissues (P < 0.001). Functionally, SPC21 knockdown promoted cell growth, migration, and invasion. Further analyses showed that SPC21 inactivated Akt signaling, and the Akt inhibitor MK-2206 blocked the tumor-promoting effects of SPC21 knockdown. Conclusions SPC21 plays a tumor suppressor role in LUAD cells by targeting the PTEN-PI3K/Akt axis and might be used as a prognostic indicator and therapeutic target in LUAD patients.

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“…Multiple lines of evidence demonstrated that GALNT2 was dysregulated in several solid tumors, such as glioma [ 17 ], neuroblastoma [ 18 ], gastric adenocarcinoma [ 19 ], oral squamous cell carcinoma [ 20 ], and hepatocellular carcinoma [ 21 ]. Several recent independent studies revealed that GALNT2 was overexpressed in lung adenocarcinoma [ 22 , 23 ]. The present study, however, showed that GALNT2 was upregulated in all subtypes of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer

Tian

Leng

et al. 2022

Cell Mol Biol Lett

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Background N-Acetylgalactosaminyltransferases (GALNTs), the enzymes that initiate mucin-type O-glycosylation, are closely associated with tumor occurrence and progression. However, a comprehensive analysis of GALNTs in non-small cell lung cancer (NSCLC) is lacking. Methods The expression profiles and prognostic values of the GALNT family members in NSCLC were analyzed using publicly available databases. Gain- and loss-of-function experiments were applied to assess the biological function of GALNT2 in NSCLC. High-throughput sequencing and bioinformatics approaches were employed to uncover the regulatory mechanism of GALNT2. Results Among the family members of GALNTs, only GALNT2 was frequently overexpressed in NSCLC tissues and was positively correlated with poor prognosis. In vitro assays showed that GALNT2 knockdown repressed NSCLC cell proliferation, migration, and invasion, but induced apoptosis and cell cycle arrest. Correspondently, GALNT2 overexpression exerted the opposite effects. In vivo experiments demonstrated that knockdown of GALNT2 restrained tumor formation in nude mice. Mechanistic investigations revealed that GALNT2 modified the O-glycosylation of ITGA5 and affected the activation of the PI3K/Akt and MAPK/ERK pathways. Further studies showed that miR-30d was a negative regulator of GALNT2. Conclusions These findings suggest that GALNT2 is an oncogene in NSCLC and has the potential as a target for NSCLC therapy.

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GALNT2 promotes cell proliferation, migration, and invasion by activating the Notch/Hes1-PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma

Cited by 20 publications

References 26 publications

Development and validation of endoplasmic reticulum stress-related eight-gene signature for predicting the overall survival of lung adenocarcinoma

Development and validation of endoplasmic reticulum stress-related eight-gene signature for predicting the overall survival of lung adenocarcinoma

Signal peptidase 21 suppresses cell proliferation, migration, and invasion via the PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma

The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer

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