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

Abstract

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 ...

MicroRNA-362-3p Inhibits Migration and Invasion via Targeting BCAP31 in Cervical Cancer

“…Further GSEA analysis showed that BCAP31 may participate in multiple biological processes, such as protein transport, metabolism and organelle organization. We have found in previous studies that BCAP31 may regulate the migration and invasion ability of cancer cells by regulating the expression of cytoskeletal proteins, such as Drebrin, M-RIP, SPECC1, Nexilin, and F-actin (Dang et al, 2018;Wang et al, 2020). These results are consistent with our GSEA analysis results.…”

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

“…There are reports that BAP31 promotes proliferation and metastasis in multiple cancers (Dang et al, 2018;Wang et al, 2019Wang et al, , 2020Xu et al, 2019). In the current study, we have initially illustrated that BAP31 promoted HCC migration, invasion and metastasis both in vitro and in vivo.…”

“…There are reports that BAP31 knockdown reduces expression level of TGF-β1, MMP-2, MMP-9, ROCK1, α-SMA, Vimentin and N-cadherin in cervical cancer (Wang et al, 2019), and BAP31 affects F-actin distribution to promote migration and invasion of lung cancer cells (Wang et al, 2020). Recent study also suggests that miR-362 can inhibit tumor progression via SNAIL1) and E-cadherin (CDH1) mRNA expression in Li-7 and Huh7 cell, which were divided into four groups: vector, BAP31 (DMSO-control), BAP31 (MK2206 2.5 µM) and BAP31 (MK2206 5 µM).…”

Application of two-dimensional difference gel electrophoresis to identify protein changes between center, margin, and adjacent non-tumor tissues obtained from non-small-cell lung cancer with adenocarcinoma or squamous cell carcinoma subtype

“…KRT8 was used for cancer prognosis, including for ADC patients [ 192 , 193 ], whereas KRT10 was found to be a useful biomarker for the treatment response in lung cancer [ 194 ]. Keratins appeared to be subjected to post-translational modifications when they were expressed in tumors [ 195 , 196 ].…”