The expression of PEBP4 protein in lung squamous cell carcinoma

Abstract

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.

Silencing of Human Phosphatidylethanolamine-Binding Protein 4 Enhances Rituximab-Induced Death and Chemosensitization in B-Cell Lymphoma

“…hPEBP4 is highly expressed in several solid neoplasms such as human breast cancer, prostate cancer, colorectal cancer and lung cancer [14]–[17], but whether this is true for hematologic malignancies remains undetermined. Hence, we investigated the expression pattern of hPEBP4 in clinical specimens of normal and tumor lymph node tissue using tissue microarrays.…”

“…RKIP/PEBP1 is pro-apoptotic [41]–[43] while hPEBP4 is anti-apoptotic[15]–[17], [19]–[20]. Recently, RKIP has been implicated as a metastatic suppressor for prostate cancer and breast cancer [44], [45] while hPEBP4 overexprression positively corelated with the metastasis of lung squamous cell carcinomas and colorectal cancer [14], [18]. We also found silencing of hPEBP4 enhanced the the RKIP expression in the Raji cells (data now shown), indicating the regulation between the expression of RKIP and hPEBP4 via unknown mechanisms.…”

“…hPEBP4 is preferentially expressed in several cancers, including breast cancer, prostate cancer, lung squamous cell carcinoma and colorectal cancer [14]–[19]. Silencing of hPEBP4 sensitizes the cancer cells to TNF-α/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by increasing activation of JNK (c-Jun N-terminal kinase) and the Raf-1/MEK/ERK pathway, indicating that hPEBP4 is a candidate target molecule [14]–[17]. Recently, Qiu et al have indentified IOI-42 as the first chemical inhibitor of hPEBP4 and have shown that IOI-42 can sensitize tumor cells to TNF-α and TRAIL-mediated apoptosis by targeting hPEBP4 [20].…”

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

“…PEBP4 has been reported to be involved in the tumor development and metastasis of various cancers [11]. For example, PEBP4 has been reported to be upregulated in pancreatic ductal adenocarcinoma (PDAC), and knockdown of PEBP4 has been shown to result in the attenuation of cancer cell growth, migration, and metastasis of PDAC cancer cells [10].…”

Knockdown of PEBP4 inhibits human glioma cell growth and invasive potential via ERK1/2 signaling pathway

“…Different from other members of the PEBP family, PEBP4 contains a typical phosphatidylethanolamine‐binding domain and functions as an anti‐apoptotic protein. PEBP4 is highly expressed in various human malignancies, such as glioma, colorectal cancer, and lung cancer, playing an important role in tumor formation and progression . Our previous study revealed that PEBP4 expression is significantly upregulated in human glioma compared with normal brain tissue, and immunohistochemistry analysis indicated that PEBP4 expression is positively correlated with the tumor grade and prognosis in patients with gliomas, suggesting a possible involvement of PEBP4 in the tumorigenesis and progression of glioma .…”