Re‐expression of<i><scp>L</scp>actotransferrin</i>, a candidate tumor suppressor inactivated by promoter hypermethylation, impairs the malignance of oral squamous cell carcinoma cells.

Zhang, Jie; Ling, Tianyou; Wu, Hanjiang; Wang, Kai

doi:10.1111/jop.12279

Cited by 11 publications

(14 citation statements)

References 33 publications

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“…At odds with these findings, a negative correlation between endogenous hLf expression and cancer incidence was demonstrated in different cancer cell lines, all showing a marked down-regulation of hLf transcript [103][104][105]. Lf gene silencing in cancer cells was found to be related to different molecular mechanisms, including promoter and gene hyper-methylation or direct alteration of the gene sequence [106][107][108]. Interestingly, Zhang and colleagues showed that the restoration of hLf gene expression through the use of a methyltransferase inhibitor impaired cancer cell growth and metastasis in a model of oral squamous cell carcinoma [108].…”

Section: Lactoferrin and Cancermentioning

confidence: 99%

“…Lf gene silencing in cancer cells was found to be related to different molecular mechanisms, including promoter and gene hyper-methylation or direct alteration of the gene sequence [106][107][108]. Interestingly, Zhang and colleagues showed that the restoration of hLf gene expression through the use of a methyltransferase inhibitor impaired cancer cell growth and metastasis in a model of oral squamous cell carcinoma [108]. Generally, hLf and bLf have been shown to exert anti-cancer activity for both tumor prevention and treatment [18,109].…”

Section: Lactoferrin and Cancermentioning

confidence: 99%

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Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

et al. 2020

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Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radioand chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies.

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Section: Lactoferrin and Cancermentioning

confidence: 99%

Section: Lactoferrin and Cancermentioning

confidence: 99%

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

et al. 2020

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“…In the current study, low expression of LTF gene increases the risk of metastasis in ccRCC. Previous studies have reported that LTF regulated the risk of metastasis of soft tissue sarcoma, 16 oral squamous cell carcinoma 17 and nasopharyngeal carcinoma (NPC). 19,24 LTF was considered as a candidate tumor susceptibility suppressor gene located at 3p21.31-21.2 that could negatively regulate the development and metastasis of NPC 25 by inducing cell cycle G1/S arrest, and modulating the mitogen-activated protein kinase (MAPK) and Akt signaling pathways.…”

Section: Dovepressmentioning

confidence: 99%

<p>Co-Expression Network Analysis Identified LTF in Association with Metastasis Risk and Prognosis in Clear Cell Renal Cell Carcinoma</p>

Yuan

Zhang

et al. 2020

OTT

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Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer in adults. The 5-year survival rate of patients with advanced ccRCC is less than 30%. Lack of potential biomarkers for treatment and prognosis is a limitation for early diagnosis and treatment of ccRCC. Methods: We collected microarray profiles of 39 ccRCC and matched normal samples to identify differential expression genes (DEGs). Then, a weighted gene co-expression network analysis (WGCNA) was constructed to identify gene modules associated with the metastasis in ccRCC. The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (HPA, https://www.proteinatlas.org/) database were used for verification set. Finally, we used biological experiments to preliminary investigate the impact of LTF on the tumor biological behavior of ccRCC, including proliferation, migration, invasion, and apoptosis. Results: A total of 15 genetic modules were identified, and the light-green module is considered the most relevant to tumor metastasis. (P = 0.02, R 2 = −0.4). Protein-protein interaction (PPI) network was performed to identify the hub nodes in the light-green module. Finally, combining the results of PPI, WGCNA and DEGs, lactotransferrin (LTF) gene was regarded as "real" hub genes for cancer metastasis risk. LTF was subsequently validated using the TCGA database. Immunohistochemistry confirmed that the expression of LTF in ccRCC tumor tissue was significantly lower than that in normal tissue based on the HPA database. Intriguingly, patients with low expression of LTF had lower survival rates (HR = 0.66, 95% CI: 0.49-0.89, P = 0.0067), the expression level of the sample was negatively correlated with tumor stage (P = 0.0385), and patients with low expression of LTF gene were more likely to have distant metastasis (P = 0.038). Overexpression of LTF inhibited the proliferation, migration, invasion and promoted apoptosis of human ccRCC cells in vitro. Conclusion: LTF might be a novel prognostic biomarker for ccRCC.

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“…METTL7A and LTF are reported to act as tumor suppressor genes ( Qi et al, 2017 ; Zhang et al, 2011 ; Zhang et al, 2015 ). Similarly, our findings showed that the expressions of METTL7A and LTF were decreased in OS samples.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential gene signatures associated with osteosarcoma by integrated bioinformatics analysis

Jia¹,

Liu²,

Han

et al. 2021

PeerJ

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Background Osteosarcoma (OS) is the most primary malignant bone cancer in children and adolescents with a high mortality rate. This work aims to screen novel potential gene signatures associated with OS by integrated microarray analysis of the Gene Expression Omnibus (GEO) database. Material and Methods The OS microarray datasets were searched and downloaded from GEO database to identify differentially expressed genes (DEGs) between OS and normal samples. Afterwards, the functional enrichment analysis, protein–protein interaction (PPI) network analysis and transcription factor (TF)-target gene regulatory network were applied to uncover the biological function of DEGs. Finally, two published OS datasets (GSE39262 and GSE126209) were obtained from GEO database for evaluating the expression level and diagnostic values of key genes. Results In total 1,059 DEGs (569 up-regulated DEGs and 490 down-regulated DEGs) between OS and normal samples were screened. Functional analysis showed that these DEGs were markedly enriched in 214 GO terms and 54 KEGG pathways such as pathways in cancer. Five genes (CAMP, METTL7A, TCN1, LTF and CXCL12) acted as hub genes in PPI network. Besides, METTL7A, CYP4F3, TCN1, LTF and NETO2 were key genes in TF-gene network. Moreover, Pax-6 regulated four key genes (TCN1, CYP4F3, NETO2 and CXCL12). The expression levels of four genes (METTL7A, TCN1, CXCL12 and NETO2) in GSE39262 set were consistent with our integration analysis. The expression levels of two genes (CXCL12 and NETO2) in GSE126209 set were consistent with our integration analysis. ROC analysis of GSE39262 set revealed that CYP4F3, CXCL12, METTL7A, TCN1 and NETO2 had good diagnostic values for OS patients. ROC analysis of GSE126209 set revealed that CXCL12, METTL7A, TCN1 and NETO2 had good diagnostic values for OS patients.

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Re‐expression ofLactotransferrin, a candidate tumor suppressor inactivated by promoter hypermethylation, impairs the malignance of oral squamous cell carcinoma cells.

Cited by 11 publications

References 33 publications

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

<p>Co-Expression Network Analysis Identified LTF in Association with Metastasis Risk and Prognosis in Clear Cell Renal Cell Carcinoma</p>

Identification of potential gene signatures associated with osteosarcoma by integrated bioinformatics analysis

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