Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via Integrin/EGFR-ERK/MAPK signaling pathway

Sheng, Weiwei; Chen, Chuanping; Dong, Ming; Wang, Guosen; Zhou, Jianping; He, Song; Li, Yang; Zhang, Jian; Ding, Shuangning

doi:10.1038/cddis.2017.547

Cited by 136 publications

(119 citation statements)

References 58 publications

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“…The MAPK signaling pathway plays a role in EMT of the various kinds of epithelial cells and includes JNK, p38 MAPK and ERK [23-25]. We observed a robust increase of the phospho-p38, and phospho-ERK in the HG-treated NRK-52E cells compared with the control group (Fig.…”

Section: Resultsmentioning

confidence: 54%

Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Zhang

Liang³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Evidence from our and other groups has demonstrated that zinc transporter 7 in SLC30 family (ZnT7) inhibited epithelial-to-mesenchymal transition (EMT) and apoptosis in rat peritoneal mesothelial cells (RPMCs) under high glucose (HG) concentration. In the present study, we investigated the effect of ZnT7 on EMT of renal tubular epithelial cells (RTECs) in an in vitro model of diabetic nephropathy (DN). Methods: A dual-fluorescent staining protocol was used for detection of ZnT7 in a normal rat kidney tubular epithelial cell line (NRK-52E cells). EMT was induced with HG (30 mM). NRK-52E cells were transfected with plasmids codifying for hZnT7-EGFP and interfering RNA for determination of the effect of ZnT7 over-expression and silencing, respectively. Expression of ZnT7, activation of the MAPK/ERK and TGF-β/Smad pathways were analyzed with by means of Western blot. Results: ZnT7 was localized in the perinuclear region and Golgi apparatus. In HG-induced EMT of NRK-52E cells, ZnT7 was up-regulated. Over-expression of ZnT7 led to inhibition of HG-induced EMT, while knock-down of ZnT7 increased EMT. Furthermore, knock-down of ZnT7 and increased HG-induced EMT was accompanied by activation of the MAPK/ERK and TGF-β/Smad pathways. Conclusion: The present study provides evidence that ZnT7 has a protective effect over EMT of RTECs in DN and suggests that the inhibition of HG-induced EMT may be achieved through the MAPK/ERK and TGF-β/Smad pathways. Thereby, ZnT7 could be a potential target for translation medicine and prevention program in DN.

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Section: Resultsmentioning

confidence: 54%

Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Zhang

Liang³

et al. 2018

Kidney Blood Press Res

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“…Numerous studies have shown that specific molecules can affect the tumorigenesis, progression, incursion as well as migration of pancreatic cancer by participating in the regulation of JAK/STAT pathway . MAPKKK cascade is the key molecule in the MAPK pathway, and MAPK pathway can be incorporated to control cell propagation, invasion, migration, apoptosis, tumorigenesis, and progression of pancreatic tumor, as well as chemotherapy response and clinical outcomes . For the two drugs that were identified in our current study, no previous studies have identified their functions on cancer treatment.…”

Section: Discussionmentioning

confidence: 88%

“…[41][42][43][44] MAPKKK cascade is the key molecule in the MAPK pathway, and MAPK pathway can be incorporated to control cell propagation, invasion, migration, apoptosis, tumorigenesis, and progression of pancreatic tumor, as well as chemotherapy response and clinical outcomes. [45][46][47][48][49][50][51] For the two drugs that were identified in our current study, no previous studies have identified their functions on cancer treatment. These two drugs as the targeted agents for pancreatic cancer remain to be confirmed by further research as well as clinical trials.…”

Section: Discussionmentioning

confidence: 96%

Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma

Liu

Chen

et al. 2020

Cancer Medicine

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Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4‐AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple cancers. However, the clinical significance of FOXP4‐AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The goal of this study is to recognize the possible clinical significance of long noncoding RNA FOXP4‐AS1 in patients with early stage PDAC. A total of 112 patients from The Cancer Genome Atlas (TCGA) PDAC cohort, receiving RNA sequencing, were involved in the study. Survival analysis, functional mechanism, and potential small molecule drugs of target therapy of FOXP4‐AS1 were performed in this study. Survival analysis in TCGA PDAC cohort suggested that patients with high FOXP4‐AS1 expression had significantly augmented possibility of death than in PDAC patients with lower FOXP4‐AS1 expression (adjusted P = .008; adjusted HR = 2.143, 95% CI = 1.221‐3.760). In this study, a genome‐wide RNA sequencing dataset was used to identify 927 genes co‐expressing with FOXP4‐AS1 in PDAC tumor tissues. A total of 676 differentially expressed genes were identified between different FOXP4‐AS1 expression groups. Functional enrichment analysis of these genes and gene set enrichment analysis for PDAC genome‐wide RNA sequencing dataset was done. We have found that FOXP4‐AS1 may function in PDAC by participating in biological processes and pathways including oxidative phosphorylation, tricarboxylic acid cycle, classical tumor‐related pathways such as NF‐kappaB as well as Janus kinase/signal transducers in addition to activators of transcription, cell proliferation, and adhesion. In addition, we also screened two potential targeted therapeutic small molecule drugs (dimenhydrinate and metanephrine) for FOXP4‐AS1 in PDAC. In conclusion, our present study demonstrated that higher expression of FOXP4‐AS1 in PDAC tumor tissues were related with an inferior medical outcome. Through multiple genome‐wide approaches, we identified the potential molecular mechanisms of FOXP4‐AS1 in PDAC and two targeted therapeutic drugs for it.

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“…This phenomenon for GRP78 was familiar to us 20 ; however, this was the first time that BCAP31 has been associated with the differentiation and malignancy of NSCLC, which may be due to BCAP31 exhibiting stemness functionality 21 . Survival prediction efficiency of NSCLC patients improved as more markers were included, suggesting that BCAP31 might play a similar role to the other three markers in promoting cancer metastasis 22,23 .…”

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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Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via Integrin/EGFR-ERK/MAPK signaling pathway

Cited by 136 publications

References 58 publications

Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma

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

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