Annexin A5 overexpression might suppress proliferation and metastasis of human uterine cervical carcinoma cells1

Li, Xin; Ma, Wenyi; Wang, Xiaojie; Ci, Yunzhe; Zhao, Yong

doi:10.3233/cbm-171040

Cited by 16 publications

(16 citation statements)

References 33 publications

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“…Contrarily, large amounts of research demonstrated ANXA5 acts as tumor suppressor. For instance, ANXA5 can suppress cell proliferation and metastasis in uterine cervical carcinoma ( 13 ); it transfers to the mitochondria, suppressing the voltage-dependent anion channel (VDAC) oligomerization which leads to prostate cancer cell apoptosis ( 14 ). ANXA5 suppresses murine neuroblastoma cell proliferation by blotting PS which results in the enhanced T cell-dependent tumor immunity ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway

et al. 2021

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Gastric cancer is one of the most fatal diseases around the world. However, the mechanism of the development of gastric cancer is still not clarified. In addition, the anticancer drugs have cytotoxicity with different degrees. AnnexinA5, a member of the annexin family, has a great binding ability with the membrane phospholipid in a calcium dependent manner and is involved in the development of various cancers. This study aims to explore the influence of annexinA5 on human gastric cancer cells and whether it has the potential to be an auxiliary treatment to gastric cancer. In this study, the role of annexinA5 was detected from both the endogenous and the exogenous aspects on the gastric cancer cell lines MGC-803 and MKN-45. The cells were divided into a knockdown group in which RNA interference technique was used to suppress annexinA5 expression and a protein-supplementing group in which annexinA5 protein was added in the culture supernatant. After the suppression ratio of RNA interference was determined and the IC50 of annexinA5 protein was decided respectively, the cells’ proliferation was detected by MTT assay, colony formation assay, and the expression of PCNA. FCM assay and PI staining methods were applied to test cell apoptosis and necrosis. To investigate whether ANXA5 influence cell metastasis, wound healing assay and transwell assay were employed. To further detect the mechanism of annexinA5 action, the signal pathway was examined with Western Blot method. When ANXA5 gene was knocked down, cell proliferation and metastasis were promoted, while cell apoptosis was suppressed. On the other hand, after the annexinA5 protein was applied to the gastric cancer cells, cell proliferation and metastasis were inhibited, while cell apoptosis and necrosis were promoted. AnnexinA5 played its role via ERK signal pathway. ANXA5 acted as tumor suppressor gene in the gastric cancer by suppressing ERK signal pathway and has the potentiality to be an auxiliary anticancer agent.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway

et al. 2021

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“…In support of this our speculation, Kang et al showed that the combined administration of metformin and Sorafenib significantly inhibits the recurrence and metastasis of primary liver cancer in HCC patients, after surgical resection [64]. Moreover, we observed that METF stimuli increased annexin A5 protein expression (Figure 6(c)): recent data indicate how the upregulation of this protein ameliorates antitumoral response, acting on cell cycle regulators [12, 13]. We speculated that METF, acting on annexin A5, could represent a novel coadjuvant in cancer therapy.…”

Section: Discussionsupporting

confidence: 83%

“…Molecular target therapy is now developing as a novel anticancer modality and seems to be a promising way for prolonging advanced HCC patient survival. Insulin-like growth factor (IGF) signaling is specifically required for hepatocyte malignant transformation and HCC progression [65, 66], especially the IGF-I receptor (IGF-IR) [13] and IGF-II expression in hepatocarcinogenesis [46, 65]. IGF-IR stimulates growth of HCC cells through the activation of the IGF-II/IGF-IR pathway: this receptor is not expressed in healthy mature hepatocytes, whereas HCC cells exhibit abnormal activation.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, Jeong et al have demonstrated that annexin A5 plays an important role as a mediator of cisplatin antitumorigenesis action [12]. Recently, Li et al have demonstrated that annexin A5 overexpression in the uterine cervical carcinoma might negatively regulate cell proliferation [13]. Thus, these studies suggest how induction of annexin A5 could be a promising target in cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

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Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis

Vacante

Senesi

Montesano

et al. 2019

International Journal of Endocrinology

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Background and Aims Hepatocellular carcinoma (HCC) is the common tumor of the liver. Unfortunately, most HCC seem to be resistant to conventional chemotherapy and radiotherapy. The poor efficacy of antitumor agents is also due, at least in part, to the inefficient drug delivery and metabolism exerted by the steatotic/cirrhotic liver that hosts the tumor. Thus, novel approaches in chemotherapy may be needed to improve the survival rate in patients with HCC. Metformin (METF) has been found to lower HCC risk; however, the mechanisms by which METF performs its anticancer activity are not completely elucidated. Previous studies have showed METF action on growth inhibition in the liver in a dose/time-dependent manner and its antitumor role by targeting multiple pathways. We investigated molecular effects of METF in an in vitro human hepatoma model (HepG2), studying cell cycle regulators, tumorigenesis markers, and insulin-like growth factor (IGF) axis regulation. Materials and Methods HepG2 cells were treated with METF (400 μM) for 24, 48, and 72 hours. METF action on cell cycle progression and cellular pathways involved in metabolism regulation was evaluated by gene expression analysis, immunofluorescence, and Western blot assay. Results By assessing HepG2 cell viability, METF significantly decreased growth cell capacity raising KLF6/p21 protein content. Moreover, METF ameliorated the cancer microenvironment reducing cellular lipid drop accumulation and promoting AMPK activity. The overexpression of IGF-II molecule and the IGF-I receptor that plays a main role in HCC progression was counteracted by METF. Furthermore, the protein content of HCC principal tumor markers, CK19 and OPN, linked to the metastasis process was significantly reduced by METF stimulus. Conclusion Our data show that METF could suppress HepG2 proliferation, through induction of cell cycle arrest at the G0/G1 phase. In addition, METF effect on the cancer microenvironment and on the IGF axis leads to the development of new METF therapeutic use in HCC treatment.

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“…Potential mechanisms for this include effects of ANXA5 on regulation of genes implicated in cell motility (including S100A4 , TIMP3 and RHOC ), 41 activation of PI3K–Akt–mammalian target of rapamycin signalling leading to tumour cell proliferation, 37 promotion of migration and invasion via upregulation of matrix metalloproteinases 2 and 9, 37 and effects on integrin signalling and mitogen‐activated protein kinase kinase–extracellular signal‐regulated kinase pathways 42 . Conversely, ANXA5 may have a protective role in some cancers because ANXA5 overexpression can inhibit proliferation and metastasis, including in uterine and cervical carcinoma cell lines 43 . In addition, administration of ANXA5 in a murine model of human papillomavirus 16‐associated cancer augmented antitumour immunity by binding to phosphatidylserine externalized by apoptotic tumour cells, which enhanced the immunogenicity of tumour antigens 44 …”

Section: Discussionmentioning

confidence: 99%

Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs*

et al. 2020

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Summary Background Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers capable of metastasizing. Proteomic analysis of cSCCs can provide insight into the biological processes responsible for metastasis, as well as future therapeutic targets and prognostic biomarkers. Objectives To identify proteins associated with development of metastasis in cSCC. Methods A proteomic‐based approach was employed on 105 completely excised, primary cSCCs, comprising 52 that had metastasized (P‐M) and 53 that had not metastasized at 5 years post‐surgery (P‐NM). Formalin‐fixed, paraffin‐embedded cSCCs were microdissected and subjected to proteomic profiling after one‐dimensional (1D), and separately two‐dimensional (2D), liquid chromatography fractionation. Results A discovery set of 24 P‐Ms and 24 P‐NMs showed 144 significantly differentially expressed proteins, including 33 proteins identified via both 1D and 2D separation, between P‐Ms and P‐NMs. Several differentially expressed proteins were also associated with survival in SCCs of other organs. The findings were verified by multiple reaction monitoring on six peptides from two proteins, annexin A5 (ANXA5) and dolichyl‐diphosphooligosaccharide–protein glycosyltransferase noncatalytic subunit (DDOST), in the discovery group and validated on a separate cohort (n = 57). Increased expression of ANXA5 and DDOST was associated with reduced time to metastasis in cSCC and decreased survival in cervical and oropharyngeal cancer. A prediction model using ANXA5 and DDOST had an area under the curve of 0·93 (confidence interval 0·83–1·00), an accuracy of 91·2% and higher sensitivity and specificity than cSCC staging systems currently in clinical use. Conclusions This study highlights that increased expression of two proteins, ANXA5 and DDOST, is significantly associated with poorer clinical outcomes in cSCC.

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Annexin A5 overexpression might suppress proliferation and metastasis of human uterine cervical carcinoma cells1

Abstract: ANXA5 overexpression in the uterine cervical carcinoma might play important roles in cell proliferation and metastasis of uterine cervical cancer cells and act as an anti-cancer gene in uterine cervical cancer.

Cited by 16 publications

References 33 publications

RETRACTED: AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway

RETRACTED: AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway

Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis

Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs*

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