Annexin A3 as a Potential Target for Immunotherapy of Liver Cancer Stem-Like Cells

Pan, Qiu Zhong; Pan, Ke; Wang, Qi Jing; Weng, De Sheng; Zhao, Jing; Zheng, Hai Xia; Zhang, Xiao Fei; Jiang, Shan; Lv, Lin; Tang, Yan; Li, Yong Qiang; He, Jia; Liu, Qing; Chen, Chang Long; Zhang, Hong Xia; Xia, Jian Chuan

doi:10.1002/stem.1850

Cited by 61 publications

(44 citation statements)

References 52 publications

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“…Studies have demonstrated that ANXA3 is a potential biomarker for carcinogenesis, metastasis and resistance to chemotherapy in many cancers such as ovarian cancer [11], gastric cancer [12], breast cancer [13, 14] and liver carcinoma [15, 16]. But there is hardly any investigation of its role in CRC.…”

Section: Discussionmentioning

confidence: 99%

High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers

Zhong

et al. 2016

Oncotarget

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Proteins, as executives of genes' instructions, are responsible for cellular phenotypes. Integrating proteomics with gene microarray, we conducted this study to identify potential protein biomarkers of colorectal cancer (CRC). Isobaric tags with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between paired CRC and adjacent normal mucosa. Meanwhile, Affymetrix U133plus2.0 microarrays were used to perform gene microarray analysis. Verification experiments included immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay (ELISA) of selected proteins. Overall, 5469 differentially expressed proteins were detected with iTRAQ-MS from 24 matched CRC and adjacent normal tissues. And gene microarray identified 39859 differential genes from 52 patients. Of these, 3083 differential proteins had corresponding differentially expressed genes, with 245 proteins and their genes showed >1.5-fold change in expression level. Gene ontology enrichment analysis revealed that up-regulated proteins were more involved in cell adhesion and motion than down-regulated proteins. In addition, up-regulated proteins were more likely to be located in nucleus and vesicles. Further verification experiments with IHC confirmed differential expression levels of 5 proteins (S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1) between CRC and normal tissues. Besides, western blot showed a stepwise increase of annexin A3 abundance in normal colorectal mucosa, adenoma and CRC tissues. ELISA results revealed significantly higher serum levels of S100 calcium-binding protein A9 and annexin A3 in CRC patients than healthy controls, validating diagnostic value of these proteins. Cell experiments showed that inhibition of annexin A3 could suppress CRC cell proliferation and aggressiveness. S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1 were probably potential biomarkers of colorectal cancer. Annexin A3 was a potentially valuable therapeutic target of CRC.

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Section: Discussionmentioning

confidence: 99%

High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers

Zhong

et al. 2016

Oncotarget

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“…Overexpression ANXA3 is associated with cancer [23–24]. ANXA3 has been reported that increased in HCC [24] and as a potential target for immunotherapy of liver cancer stem-like cells [25].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of ANXA3 is an independent prognostic indicator in gastric cancer and its depletion suppresses cell proliferation and tumor growth

Wang

2016

Oncotarget

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BackgroundGastric cancer (GC) is one of the most common malignancies worldwide. Tumour metastasis is one of the leading causes of death in GC patients. This study aims to investigate the significance of ANXA3 expression and the mechanism by which ANXA3 is involved in the epithelial–mensenchymal transition (EMT) of gastric cancer cells.ResultsOur results confirmed that ANXA3 was high expression at the mRNA and protein level in GC cancer tissues and the majority of GC cell lines. In clinicopathological analysis, we found that increased expression of ANXA3 in tumors was closely associated with a poor prognosis. Xogenous ANXA3 transduction promoted proliferation, clone formation, migration, and invasion. Small interfering RNA silencing of ANXA3 inhibited these processes. Silence of ANXA3 inhibited tumorigenicity in vivo. Additionally, ANXA3 expression is associated with the epithelial–mesenchymal transition.MethodsFirstly, we investigated the ANXA3 expression on mRNA and protein level with RT-PCR and Western blot. Secondly, 183 GC patients tissues were used the to evaluate the clinicopathological characteristics and prognosis through immunohistochemistry. Furthermore, The functions of ANXA3 were analyzed in the cell proliferation, Colony Formation, migration, invasion and apoptosis of GC cell lines.ConclusionsOur research suggests that ANXA3 plays important roles in gastric cancer carcinogenesis and metastasis, and provides a valuable prognostic marker and potential target for treatment of gastric cancer patients.

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“…It was reported that the expression of Anxa3 was positively correlated with Ki-67 and Bcl-2 expression in gastric cancer [11]. In hepatocellular carcinoma, Anxa3-mediated maintenance of cancer stem-like cells activity was revealed to most likely involve the HIF-1 α /Notch pathway [14]. Multiple lines of evidence have indicated that Anxa3 expression might be a potential prognostic marker for tumor patients and an indicator of tumor development, invasion, and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Annexin A3 Knockdown Suppresses Lung Adenocarcinoma

Liu

Zhang

et al. 2016

Analytical Cellular Pathology

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Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin.

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Annexin A3 as a Potential Target for Immunotherapy of Liver Cancer Stem-Like Cells

Cited by 61 publications

References 52 publications

High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers

High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers

Overexpression of ANXA3 is an independent prognostic indicator in gastric cancer and its depletion suppresses cell proliferation and tumor growth

Annexin A3 Knockdown Suppresses Lung Adenocarcinoma

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