Enhanced expression of cell-surface B-cell receptor-associated protein 31 contributes to poor survival of non-small cell lung carcinoma cells

Seo, Se-Ri; Lee, Hyun Min; Choi, Hong Seo; Kim, Won‐Tae; Cho, Eun‐Wie; Ryu, Chun Jeih

doi:10.1371/journal.pone.0188075

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…As a cancer/testis antigen, BAP31 has been correlated with patient survival in multiple kinds of cancer (Dang et al, 2018;Xu et al, 2019). BAP31 was up-regulated in cervical cancer, malignant melanomas and lung carcinomas and its high expression indicated a poor prognosis (Yu et al, 2015;Seo et al, 2017;Dang et al, 2018). In the present study, we have elucidated that BAP31 was up-regulated in HCC compared to normal tissues and high BAP31 expression contributed to poor prognosis, which suggested BAP31 might serve as a potential prognostic factor in HCC.…”

Section: Discussionsupporting

confidence: 50%

B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma

Liu

et al. 2021

Front. Mol. Biosci.

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Hepatocellular carcinoma (HCC) is one of the most lethal cancer worldwide, characterized with high heterogeneity and inclination to metastasize. Emerging evidence suggests that BAP31 gets involved in cancer progression with different kinds. It still remains unknown whether and how BAP31 plays a role in HCC metastasis. Epithelial–mesenchymal transition (EMT) has been a common feature in tumor micro-environment, whose inducer TGF-β increased BAP31 expression in this research. Elevated expression of BAP31 was positively correlated with tumor size, vascular invasion and poor prognosis in human HCC. Ectopic expression of BAP31 promoted cell migration and invasion while BAP31 knockdown markedly attenuated metastatic potential in HCC cells and mice orthotopic xenografts. BAP31 induced EMT process, and enhanced the expression level of EMT-related factor Snail and decreased contents and membrane distribution of E-cadherin. BAP31 also activated AKT/β-catenin pathway, which mediated its promotional effects on HCC metastasis. AKT inhibitor further counteracted the activated AKT/β-catenin/Snail upon BAP31 over-expression. Moreover, silencing Snail in BAP31-overexpressed cells impaired enhanced migratory and invasive abilities of HCC cells. In HCC tissues, BAP31 expression was positively associated with Snail. In conclusion, BAP31 promotes HCC metastasis by activating AKT/β-catenin/Snail pathway. Thus, our study implicates BAP31 as potential prognostic biomarker, and provides valuable information for HCC prognosis and treatment.

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Section: Discussionsupporting

confidence: 50%

B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma

Liu

et al. 2021

Front. Mol. Biosci.

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“…The cleaved BCAP31 fragment, p20, is a potent inducer of apoptosis when expressed ectopically 36 . Therefore, the enhanced expression of BCAP31 could contribute to the poor survival of NSCLC cells 37 , which should benefit patients. However, full-length BCAP31 inhibits caspase activity 38 , and in cancer, apoptosis-resistance mechanisms are used to evade cell death 39 .…”

Section: Discussionmentioning

confidence: 99%

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

Wang

Jiang

et al. 2020

Sci Rep

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Non-small-cell lung cancer (NSCLC) represents most of lung cancers, is often diagnosed at an advanced metastatic stage. Therefore, exploring the mechanisms underlying metastasis is key to understanding the development of NSCLC. The expression of B cell receptor-associated protein 31 (BCAP31), calreticulin, glucose-regulated protein 78, and glucose-regulated protein 94 were analyzed using immunohistochemical staining of 360 NSCLC patients. It resulted that the high-level expression of the four proteins, but particularly BCAP31, predicted inferior overall survival. What's more, BCAP31 was closely associated with histological grade and p53 status, which was verified by seven cohorts of NSCLC transcript microarray datasets. Then, three NSCLC cell lines were transfected to observe behavior changes BCAP31 caused, we found the fluctuation of BCAP31 significantly influenced the migration, invasion of NSCLC cells. To identify the pathway utilized by BCAP31, Gene Set Enrichment Analysis was firstly performed, showing Akt/m-TOR/p70S6K pathway was the significant one, which was verified by immunofluorescence, kinase phosphorylation and cellular behavioral observations. Finally, the data of label-free mass spectroscopy implied that BCAP31 plays a role in a fundamental biological process. This study provides the first demonstration of BCAP31 as a novel prognostic factor related to metastasis and suggests a new therapeutic strategy for NSCLC.Lung cancer is one of the most prevalent neoplasms and the leading cause of cancer-related death worldwide, being responsible for nearly one in five cases 1 . Non-small-cell lung cancer (NSCLC) contributes to 85% of lung cancer cases. Owing to the absence of clinical symptoms and effective screening programs, most lung cancers are diagnosed at an advanced stage with metastasis. Targeted immunotherapy, including anti-angiogenic and checkpoint monoclonal antibodies or tyrosine kinase inhibitors, demonstrates better efficacy than traditional surgical treatment and radio-chemotherapy, although drug resistance and tumor heterogeneity remain significant problems, and metastasis remains the major cause of mortality 2 .It is therefore important to identify efficient symbolic markers of metastasis and therapeutic targets for NSCLC. Given the aberrant expression of specific genes in a variety of cancer types, restricted in testis or selected in normal tissue, cancer-testis antigens (CTAs) have emerged as efficient specific tumor targets which spare normal tissue from incurring damage during treatment 3 . Originally described in patients with malignant melanoma 4 , CTAs have been identified as biomarkers for a diverse range of cancers, including NSCLC 5 . Their expression is often coordinated 6 , and associated with poor clinical outcome 7 and advanced stage 8 , particularly metastasis 9 .with histological grade (p = 0.0009) and p53 status (p = 0.0058; Supplementary Table S1). However, there was no correlation between BCAP31 mRNA expression and NSCLC prognosis, which was inconsistent with our protein ...

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“…B-cell receptor-associated protein 31 (BAP31), an important apoptosis regulator for extrinsic apoptosis induction in the ER membrane, plays ar ole as am olecular chaperone for the newly synthesized transmembrane proteins. [18] LPCAT3 plays am ajor role in phospholipidm etabolism in the liver and intestine. [19] It was reported that TM9SF3 participates in tumor invasion and serves as ap rognostic factor,a nd might be ap otential diagnostic and therapeutic targetf or scirrhoustype gastric cancer.…”

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confidence: 99%

Cell‐ and Tissue‐Based Proteome Profiling and Bioimaging with Probes Derived from a Potent AXL Kinase Inhibitor

Zheng-Lin

Guo

et al. 2018

Chemistry An Asian Journal

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AXL has been defined as a novel target for cancer therapeutics. However, only a few potent and selective inhibitors targeting AXL are available to date. Recently, our group has developed a lead compound, 9im, capable of displaying potent and specific inhibition of AXL. To further identify the cellular on/off targets, in this study, competitive affinity-based proteome profiling was carried out, leading to the discovery of several unknown cellular targets such as BCAP31, LPCAT3, POR, TM9SF3, SCCPDH and CANX. In addition, trans-cyclooctene (TCO) and acedan-containing probes were developed to image the binding between 9im and its target proteins inside live cells and tumor tissues. These probes would be useful tools in the detection of AXL in various biosystems.

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Enhanced expression of cell-surface B-cell receptor-associated protein 31 contributes to poor survival of non-small cell lung carcinoma cells

Cited by 11 publications

References 27 publications

B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma

B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

Cell‐ and Tissue‐Based Proteome Profiling and Bioimaging with Probes Derived from a Potent AXL Kinase Inhibitor

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