Role of the PEBP4 protein in the development and metastasis of gastric cancer

Wu, Zijian; Liu, Bin; Zheng, Xiaojiao; Hou, Huijing; Liu, Ying

doi:10.18632/oncotarget.15255

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…Recent laboratory studies on targeted therapy have shown that PEBP4 gene knockout inhibits cell proliferation, migration, and invasion in gastric cancer cell lines 9. PEBP4 knockout significantly inhibits both phosphorylated PI3K and phosphorylated AKT in gastric cancer cells 23.…”

Section: Introductionmentioning

confidence: 99%

“…In the normal tissues, PEBP4 was mainly expressed in the heart, lung, prostate, and thyroid of mammals, and slightly expressed in liver, colon, skin, adrenal gland, and bone marrow 6. More importantly, it was commonly reported that PEBP4 highly expressed in all cancerous tissues 7–9…”

Section: Introductionmentioning

confidence: 99%

“…In a large number of treatments of malign cancers, activation of the PI3K/AKT signal pathway tended to render cells resistant to radiotherapy and chemotherapy 34–36. Other studies showed that PEBP4 participated in the activation of PI3K/AKT signal pathway, and PEBP4 seemed to be an important factor in the activation of AKT signaling pathway in cancer cells 9,37,38. Yu G. et al found that the overexpression of PEBP4 played activated roles in phosphorylation of AKT in HCC827 cells, and down-regulation of PEBP4 inhibited the phosphorylation of AKT 17.…”

Section: Introductionmentioning

confidence: 99%

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<p>The Roles And Signaling Pathways Of Phosphatidylethanolamine-Binding Protein 4 In Tumors</p>

Luo

Chen

et al. 2019

OTT

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Phosphatidylethanolamine-binding protein 4 (PEBP4) has been found to be highly expressed in many tumors and to be closely related to the proliferation, differentiation, and metastasis of tumors. PEBP4 has also been found to be involved in many canceractivated signaling pathways and to cause therapeutic resistance. In this study, we first reviewed the morphological structure and expression of PEBP4, then discussed the roles of PEBP4 in individualized treatment of some cancers, and finally explored the possibilities of cultivating PEBP4 as a therapeutic target.We also identified the main signaling pathways in which PEBP4 affects different cancers. It is here concluded that over-expression of PEBP4 can enhance the proliferation and metastasis of the cancer cells and the resistance to radiotherapy/chemotherapy in cancers.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<p>The Roles And Signaling Pathways Of Phosphatidylethanolamine-Binding Protein 4 In Tumors</p>

Luo

Chen

et al. 2019

OTT

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“…PEBP4, a member of the PEBP family, is a secreted protein widely expressed in multiple organs of the human body (18). At present, studies on PEBP4 have mostly focused on cancers (19)(20)(21)(22)(23). In addition, members of the PEBP family, such as Raf kinase inhibitor protein (RKIP) and PEBP1, can regulate microglia inflammation by inhibiting the NF-kB signaling pathway (24,25), and RKIP is known to be closely associated with ALF (26).…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte-Conditional Knockout of Phosphatidylethanolamine Binding Protein 4 Aggravated LPS/D-GalN-Induced Acute Liver Injury via the TLR4/NF-κB Pathway

Chen

Shi

et al. 2022

Front. Immunol.

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Acute liver injury (ALI) is a disease that seriously threatens human health and life, and a dysregulated inflammation response is one of the main mechanisms of ALI induced by various factors. Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein with multiple biological functions. At present, studies on PEBP4 exist mainly in the field of tumors and rarely in inflammation. This study aimed to explore the potential roles and mechanisms of PEBP4 on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALI. PEBP4 was downregulated after treatment with LPS/D-GalN in wild-type mice. PEBP4 hepatocyte-conditional knockout (CKO) aggravated liver damage and repressed liver functions, including hepatocellular edema, red blood cell infiltration, and increased aspartate aminotransferase (AST)/alanine aminotrans-ferase (ALT) activities. The inflammatory response was promoted through increased neutrophil infiltration, myeloperoxidase (MPO) activities, and cytokine secretions (interleukin-1β, IL-1β; tumor necrosis factor alpha, TNF-α; and cyclooxygenase-2, COX-2) in PEBP4 CKO mice. PEBP4 CKO also induced an apoptotic effect, including increasing the degree of apoptotic hepatocytes, the expressions and activities of caspases, and pro-apoptotic factor Bax while decreasing anti-apoptotic factor Bcl-2. Furthermore, the data demonstrated the levels of Toll-like receptor 4 (TLR4), phosphorylation-inhibitor of nuclear factor kappaB Alpha (p-IκB-α), and nuclear factor kappaB (NF-κB) p65 were upregulated, while the expressions of cytoplasmic IκB-α and NF-κB p65 were downregulated after PEBP4 CKO. More importantly, both the NF-κB inhibitor (Ammonium pyrrolidinedithiocarbamate, PDTC) and a small-molecule inhibitor of TLR4 (TAK-242) could inhibit TLR4/NF-κB signaling activation and reverse the effects of PEBP4 CKO. In summary, the data suggested that hepatocyte-conditional knockout of PEBP4 aggravated LPS/D-GalN-induced ALI, and the effect is partly mediated by activation of the TLR4/NF-κB signaling pathway.

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“…Most patients experience metastasis and recurrence after undergoing standard treatment that includes adjuvant chemoradiotherapy and surgery. Hence, the 5-year survival rate of GC is very poor [ 3 , 4 ]. Therefore, new prognostic tumor markers and therapeutic targets are necessary to improve the clinical outcomes for GC patients.…”

Section: Introductionmentioning

confidence: 99%

Neurofibromatosis type-1 is a prognostic indicator in human gastric carcinoma

Liu

Zhang

et al. 2017

Oncotarget

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We investigated whether the Neurofibromatosis type-1(NF1) gene was of prognostic relevance to gastric cancer (GC) patients. Immunohistochemical staining of 160 matched GC tumor and adjacent normal tissue samples showed that 58.1% (93/160) of GC samples were NF1-positive as compared to 94.4% (151/160) of normal tissue samples (χ 2 =58.05, P <0.001). qRT-PCR analysis revealed that NF1 mRNA expression is lower in GC tissues than normal tissues (χ 2 =34.23, P <0.001). Moreover, NF1 protein and mRNA levels were associated with T stage (P <0.05) and TNM (P <0.001). No association was observed with other clinicopathological parameters, including gender, age, tumor size, lymph-node metastasis, cancer differentiation and distant metastasis (all P >0.05). Kaplan-Meier analysis revealed that negative or low NF1 were associated with poor overall survival (OS) in gastric cancer patients (P<0.001). Further univariate and multivariate cox regression analysis also showed that NF1 expression was an independent risk factor of survival of GC patients. These data show that NF1 has prognostic relevance to clinical outcomes in gastric cancer patients.

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Role of the PEBP4 protein in the development and metastasis of gastric cancer

Cited by 11 publications

References 24 publications

<p>The Roles And Signaling Pathways Of Phosphatidylethanolamine-Binding Protein 4 In Tumors</p>

<p>The Roles And Signaling Pathways Of Phosphatidylethanolamine-Binding Protein 4 In Tumors</p>

Hepatocyte-Conditional Knockout of Phosphatidylethanolamine Binding Protein 4 Aggravated LPS/D-GalN-Induced Acute Liver Injury via the TLR4/NF-κB Pathway

Neurofibromatosis type-1 is a prognostic indicator in human gastric carcinoma

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