157310

PEBP4

phosphatidylethanolamine-binding protein 4;PEBP4;phosphatidylethanolamine-binding protein 4

cousin-of-RKIP 1 protein|epididymis secretory protein Li 300|protein cousin-of-RKIP 1

8p21.3

protein-coding

metastasis is responsible for more than 90% of the mortality observed among patients with breast cancer. Human phosphatidylethanolamine-binding protein 4 (hPEBP4) is a novel member of the PEBP family and functions as an anti-apoptotic molecule. Here, we found that the metastatic MDA-MB-231 breast cancer cells expressed much higher levels of hPEBP4 than the nonmetastatic MCF-7 breast cancer cells and that the expression levels of hPEBP4 were positively correlated with the metastasis of clinical breast cancer. The hPEBP4 overexpression in the MDA-MB-231 cells significantly promoted cell invasion in vitro and increased the development of lymph node metastasis in vivo. Conversely, the silencing of hPEBP4 suppressed the cell-invasive ability both in vitro and in vivo. Further investigation showed that hPEBP4 promoted the expression or activity of the metastasis-related proteinases MMP (matrix metalloproteinase) 2, MMP9 and MMP13. This hPEBP4-potentiated cell invasion and MMP expression is due to an increase in Akt activation. Knockdown of Akt restored hPEBP4-induced breast tumor metastasis in the hPEBP4-MDA-MB-231 xenograft mouse model. Moreover, we found that hPEBP4 functioned as a scaffolding molecule and enhanced the association of Akt with Src to promote Akt tyrosine phosphorylation, a prerequisite for the full activation of Akt, in a phosphatidylethanolamine-binding domain-dependent manner. Given the present information about human breast cancer, these functional data from cell culture and animal studies suggest that, in human breast cancer hPEBP4 is a novel and clinically relevant metastasis accelerator gene and may be a new diagnostic marker and therapeutic target for breast cancer metastasis.

This study aimed to investigate the expression of PEBP4 protein in colorectal carcinoma tissues and its correlation with the clinical pathology of colorectal cancer and to investigate the relationship between PEBP4 expression and the invasion and metastasis of colorectal cancer cells, which could provide an experimental basis for future biological treatments of human colorectal cancer. RT-PCR and western blot methods were applied to detect the mRNA and protein expressions, respectively, of PEBP4 in colorectal cancer tissues and normal pericarcinoma tissues, and their correlations with the tumorigenesis and development of colorectal cancer, as well as its clinical pathology, were analyzed. Using the RNA interference technology, the expression of PEBP4 was knocked down in the human colorectal cancer cell HCT116, and the changes of the invasion capability of HCT116 were monitored. The positive mRNA expression rate of PEBP4 in colorectal cancer tissue was significantly higher than that in the normal pericarcinoma tissue (p < 0.05). Also, the positive expression rate in the cancer tissues from patients with positive lymph node and distant metastasis was significantly higher than that from the patients negative for lymph node and distant metastasis (p < 0.05). The positive expression rate of PEBP4 in the cancer tissues from the patients in early stages (I, II) was significantly lower than the expression rate in patients in advanced stages (III, IV) (p < 0.05). A lower degree of differentiation in colorectal cancer corresponded to a higher positive mRNA expression rate of PEBP4 (p < 0.05). However, this was independent of the patients gender, age, and tumor size (p > 0.05). In colorectal cancer tissue, the expression of PEBP4 protein was consistent with its mRNA. Namely, PEBP4 protein expression in colorectal cancer tissues was significantly higher than that in the normal pericarcinoma tissues (p < 0.05), the expression in the cancer tissues from the patients with positive lymph node and distant metastasis was significantly higher than that from the patients who were negative for these metastases (p < 0.05), and a lower degree of differentiation in colorectal cancer corresponded to a higher TNM staging along with a higher PEBP4 protein expression (p < 0.05). After HCT116 cells transfected with PEBP4 siRNA, they showed a significantly lower expression level of PEBP4 protein (p < 0.05), and the number of cells that passed through the Transwell chamber was significantly lower compared to the non-transfected or the transfected controls (p < 0.05). The over-expression of PEBP4 protein may be related to the tumorigenesis, development, metastasis, and invasion of colorectal cancer.

The phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP family. It not only plays a role in the inhibition of the MAPK signaling pathway but also is involved in the inhibition of the JNK pathway that promotes the activation of AKT. Recent research has also shown that overexpression of PEBP4 was related to the development, invasion, and metastasis of a variety of tumors. This study aimed to investigate the correlation between PEBP4 protein expression in lung squamous cell carcinoma tissue and the clinical pathology of lung squamous cell carcinoma. Immunohistochemistry was used to detect PEBP4 expression in lung squamous cell carcinoma tissue and adjacent normal tissue from 61 patients. Western blotting was used to detect changes in the expression of PEBP4 protein between lung squamous cell carcinoma tissue and adjacent normal tissues. The correlation of PEBP4 expression and the occurrence, development, and clinical pathology of lung squamous cell carcinoma was analyzed. Of 61 patients, four patients were PEBP4 negative (-; 6.6%) and 57 patients were positive (+ to +++; 93.4%). Of those positive for PEBP4 expression, 7 patients were weakly positive (+; 11.5%), 21 patients were positive (++; 34.4%), and 29 patients were strongly positive (+++; 47.5%). PEBP4 protein was more highly expressed in lung squamous cell carcinoma tissue than in the adjacent normal lung tissue (p < 0.05). In PEBP4-positive patients, PEBP4 protein expression was significantly greater in those with lymph node metastases than in those without (p < 0.05). PEBP4 expression was significantly lower in patients at early (I and II) stages than in patients at advanced (III and IV) stages (p < 0.05). In less differentiated lung squamous cell carcinomas, PEBP4 protein expression was greater (p < 0.05); however, this was unrelated to the gender, age, or tumor size of the patient (p > 0.05). PEBP4 protein overexpression was associated with the occurrence, invasion, and metastasis of lung squamous cell carcinoma.

The goal of this study was to investigate the function of phosphatidylethanolamine-binding protein 4 (PEBP4) in invasion and metastasis of non-small cell lung cancer (NSCLC). PEBP4 mRNA and protein expression in 56 cases of NSCLC tissues were detected using RT-PCR and Western blot, and the relationship between PEBP4 expression and invasion and metastasis of NSCLC was analyzed. The change in the invasive ability of human NSCLC cell line HCC827 was observed after knocking down PEBP4 expression using RNA interference. PEBP4 mRNA and protein expression in cancer tissues of patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis (p < 0.05). PEBP4 expression significantly decreased in HCC827 cells after transfection with PEBP4 siRNA (p < 0.01), and the number of HCC827 cells that migrated through Transwell chambers was significantly lower than that of non-transfected control and transfected control cells (p < 0.01). PEBP4 over-expression may promote the invasion and metastasis of NSCLC.