Targeting LUNX Inhibits Non–Small Cell Lung Cancer Growth and Metastasis

Zheng, Xiaohu; Cheng, Min; Fu, Binqing; Fan, Xiaolei; Wang, Qing; Yu, Xiaoqing; Sun, Rui; Tian, Zhigang; Wei, Haiming

doi:10.1158/0008-5472.can-14-1831

Cited by 25 publications

(37 citation statements)

References 39 publications

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“…However, the specific function of BPIFA1 has not yet been well defined. In prior studies, its expression was detected in lung cancer (12)(13)(14)20), gastric cancer (15), salivary gland tumors (16)(17)(18)(19) and nasopharyngeal carcinoma (19). However, to the best of our knowledge, there have been no reports investigating the role of BPIFA1 in CRC.…”

Section: Discussionmentioning

confidence: 97%

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Increased expression of BPI fold-containing family A member 1 is associated with metastasis and poor prognosis in human colorectal carcinoma

Wang

Jiang

et al. 2017

Oncology Letters

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Abstract. Bactericidal or permeability-increasing protein fold-containing family A member 1 (BPIFA1) has been demonstrated to be involved in inflammatory responses in the upper airway and the progression of non-small cell lung cancer. However, the expression levels of BPIFA1 and its clinical prognostic significance in colorectal carcinoma (CRC) has not yet been elucidated. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to analyze the expression levels of BPIFA1 in CRC and normal mucosal tissues. The associations between BPIFA1 expression levels and clinicopathological characteristics, and its predictive value for prognosis in CRC, were statistically evaluated as appropriate. The expression levels of BPIFA1 were revealed to be upregulated at the transcriptional and translational levels in CRC tissues, compared with in normal mucosal tissues. A high expression level of BPIFA1 is significantly associated with invasion depth (P=0.040), lymph node metastasis (P=0.035) and distant metastasis (P=0.010). Furthermore, Kaplan-Meier analysis indicated that BIPFA1 overexpression is associated with short survival time, and the Cox proportional hazards model of risk analysis indicated that BPIFA1 is an independent prognostic factor for patients with CRC. The results of the present study suggested that BPIFA1 expression is upregulated in CRC tissues, and that an increased expression level of BPIFA1 is associated with tumor invasion, metastasis and poor prognosis, indicating that BPIFA1 may be a potential clinical prognostic predictor and therapeutic target for patients with CRC. IntroductionColorectal carcinoma (CRC) is the one of the most common types of cancer, and is the fifth leading cause of cancer-associated mortalities worldwide (1). Despite recent advancements in the surgical techniques, radiotherapy and chemotherapy available to patients diagnosed with CRC over the past several decades, the overall survival rate has not significantly improved. The existence of numerous known carcinogens and varying genetic backgrounds makes it difficult to determine which factors are most important in the development of CRC. Thus, there is a requirement to further understand the underlying molecular mechanisms and identify novel prognostic biomarkers and therapeutic targets to provide improved treatment strategies for CRC.Bactericidal or permeability-increasing protein fold-containing family A member 1 (BPIFA1) is a protein-coding gene specifically expressed in the upper airways and nasopharyngeal regions. A number of previous studies have demonstrated that BPIFA1 is involved in various physiological and pathological processes (2-19). It is considered to be involved in inflammatory responses to irritants in the upper airway (2-7). BPIFA1 may decrease mycoplasma pneumonia expression levels and inhibit interleukin 8 (8). BPIFA1 protein was also revealed to have antibacterial activity against gram-negative bacteria (9,10). The anti-inflammatory function has been associated with the regulation of macro...

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Section: Discussionmentioning

confidence: 97%

“…BPIFA1 was also revealed to be a novel marker able to distinguish gastric hepatoid adenocarcinoma from primary hepatocellular carcinoma (15). Recently, it was demonstrated that anti-LUNX antibody slowed tumor growth and metastasis and improved the survival time of mice bearing lung (20). However, little is known about BPIFA1 in CRC.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of BPI fold-containing family A member 1 is associated with metastasis and poor prognosis in human colorectal carcinoma

Wang

Jiang

et al. 2017

Oncology Letters

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“…Furthermore, the function of the anti-SPLUNC1 MAbs from our laboratory is also worthwhile to be evaluated for potential inhibitory effects on non-small cell lung cancer as showed recently in xenograft model both in vitro and in vivo. (27) …”

Section: Discussionmentioning

confidence: 99%

SPLUNC1 Is a Significant Marker in Pleural Effusion from Lung Cancer Compared to Tuberculosis

Xue

Yan

et al. 2015

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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SPLUNC1 (Short palate, lung and nasal epithelium clone1) protein is an abundant secretory product of epithelia present throughout the conducting airways. Although its function is still not fully known, most studies have focused on its defensive effect in the infection of human airways and its potential to serve as a molecular marker for lung cancer. In this study, we further evaluated the SPLUNC1 expression in patients with lung disease to explore its role in cancer or tuberculosis at the protein level. We generated a panel of antibodies by using protein from a eukaryotic expression system as the immunogen to mice. It was the panel of SPLUNC1 monoclonal antibodies that allowed us to comparatively determine SPLUNC1 protein in lung cancer and tuberculosis infection by detecting sera and pleural effusion other than airway surface. The results showed that the SPLUNC1 level was not significantly changed either from sera of lung cancer or control. There was a significant increase in pleural effusion from lung cancer when compared to tuberculosis. These results indicate that SPLUNC1 may be a useful marker for tracing lung cancer cells, based on its epithelial origin property in pleural effusion.

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“…However, similar results were rarely detected in benign lung disease and other organs (colon, liver and breast). 3 We also observed the membranous expression of LunX in NSCLC cells by immunofluorescence staining and flow cytometry. So, LunX is considered as a potential therapeutic target of NSCLC.…”

mentioning

confidence: 87%

“…We recently confirmed that the lung-specific X protein (LunX) is overexpressed in non-small-cell lung cancer (NSCLC) and promotes tumor progression, and anti-LunX antibody has the significant efficacy of anti-tumor. 3 .…”

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confidence: 99%