Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms

Deng, Min; Zhang, W; Tang, Hua; Ye, Q; Liao, Qianjin; Zhou, Yanhong; Wu, Minghua; Wang, Xiong; Zheng, Ying; Guo, Xia; Qin, Zailong; He, Wei; Zhou, Min; Xiang, Juanjuan; Li, X; Ma, Jian; Li, G

doi:10.1038/onc.2012.434

Cited by 76 publications

(64 citation statements)

References 44 publications

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“…Consistent with IPA results, DAVID analysis also indicated an enrichment of genes associated with inflammatory response, complement activation and osteogenic differentiation (Supplementary Table 2). The 99 genes down-regulated in common included LTF, a tumor suppressor and inhibitor of AKT signaling [18], and PDCD4, a tumor suppressor gene whose decreased expression has been implicated in the development and progression of several types of cancer [19][20][21][22].…”

Section: Bm-msc Exposed To Leukemia In Vivo Show Changes In Their Genmentioning

confidence: 99%

Untitled

2017

Oncotarget

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The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or null genetic backgrounds. We identified a set of genes whose expression in BM-MSC was modulated by all four AML genotypes tested. In addition, there were sets of differentially-expressed genes in AML-exposed BM-MSC that were unique to the particular AML genotype or Trp53 status. Our findings support the hypothesis that leukemia cells alter the transcriptome of surrounding BM stromal cells, in both common and genotype-specific ways. These changes are likely to be advantageous to AML cells, affecting disease progression and response to chemotherapy, and suggest opportunities for stroma-targeting therapy, including those based on AML genotype.

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Section: Bm-msc Exposed To Leukemia In Vivo Show Changes In Their Genmentioning

confidence: 99%

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2017

Oncotarget

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“…Our subsequent studies showed that LF inhibits NPC cell proliferation, induces cell cycle G 1 /S arrest, modulating MAPK signaling pathway, and cyclin D1-related proteins, 20 and inhibits NPC metastasis by suppressing AKT activity. 25 EBV is widespread in human populations, and EBV infection has been linked to the tumorigenesis of multiple cancers including NPC. 1 One important consequence of EBV infection is malignant transformation of epithelial cells, promoted by EBV-encoded protein and microRNAs.…”

Section: Lf Expression Levels Correlated Inversely With Mcp-1 and Il-mentioning

confidence: 99%

Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

Zheng

Qin²,

Ye³

et al. 2014

Laboratory Investigation

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Epstein-Barr virus (EBV) infection contributes to tumorigenesis of various human malignancies including nasopharyngeal carcinoma (NPC). EBV triggers innate immune and inflammatory responses partly through Toll-like receptor (TLR) signaling. Lactoferrin (LF), with its anti-inflammatory properties, is an important component of the innate immune system. We previously reported that LF protects human B lymphocytes from EBV infection by its ability to bind to the EBV receptor CD21, but whether LF can suppress EBV-induced inflammation is unclear. Here, we report that LF reduced synthesis of IL-8 and monocyte chemoattractant protein-1 (MCP-1) induced by EBV in macrophages via its suppression of NF-kB activity. LF interacted with TLR2 and interfered with EBV-triggered TLR2-NF-kB activation. LF inhibited the ability of TLR9 to recognize dsDNA by binding to its co-receptor CD14, which blocked the interaction between CD14 and TLR9. EBV-induced inflammation was thus aggravated in the presence of CD14. In addition, LF expression levels were significantly downregulated in NPC specimens, and correlated inversely with IL-8 and MCP-1 expression. These findings suggest that LF may suppress the EBV-induced inflammatory response through interfering with the activation of TLR2 and TLR9.

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“…The full-length LTF coding sequence entirely lacking the 3'-UTR (GeneCopoeia, Rockville, MD, USA) was subcloned into the eukaryotic expression vector pIRES (Clontech Laboratories, Inc., Mountainview, CA, USA) as previously described (20). The fusion sequences were verified by DNA sequencing using a Sanger ABI 3730xl DNA sequencer (GATC Biotech AG, Konstanz, Germany).…”

Section: Construction Of the Pires-ltf Vectormentioning

confidence: 99%

Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

Luo

Zhou

et al. 2015

Oncology Letters

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Abstract. Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. In advanced and metastatic GC, conventional chemotherapy results in limited efficacy and the average survival rate is currently approximately 10 months. Dysregulated activation of numerous genes, including zinc finger, DHHC-type containing 14; caspase-associated recruitment domain-containing protein; and Ras association domain family member 10, have been implicated in GC. The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer. However, the mechanism of the tumor suppressor function of LTF in GC remains unclear. In the present study, the expression levels of LTF in patient GC tissue samples were investigated using reverse transcription-quantitative polymerase chain reaction, and it was demonstrated that the LTF mRNA expression level in GC tissue samples was reduced by ~20-fold compared with the adjacent non-cancerous tissues (t=4.56, P<0.01). A similar trend in LTF protein expression was observed by western blot analysis. Furthermore, the present study demonstrated that the mitogen-activated protein kinase (MAPK) signaling pathway intermediates p38, c-Jun N-terminal kinase (JNK) and c-Jun were highly expressed in GC tissue samples, and indicated that LTF downregulation may be associated with the dysregulation of the MAPK signaling pathway in GC tissues. In addition, the present study indicated that LTF overexpression reduced the expression of p38, JNK2 and c-Jun in the GC cell line, SGC7901. The present study demonstrates that LTF expression is downregulated in GC tissues and that LTF may serve an important role in the dysregulation of the MAPK signaling pathway.

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Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms

Cited by 76 publications

References 44 publications

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Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

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