Clinical significance of annexin A2 downregulation in oral squamous cell carcinoma

Rodrigo, Juan P.; Lequerica-Fernández, Paloma; Rosado, Pablo; Allonca, Eva; García-Pedrero, Juana M.; Vicente, Juan Carlos de

doi:10.1002/hed.21661

Cited by 25 publications

(25 citation statements)

References 68 publications

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“…Previous research has shown that ANXA2 over-expression is correlated with poor prognosis of human gastric carcinoma [39], conventional renal cell carcinoma [40], nonsmall cell lung cancer [11,41], esophageal squamous cell carcinoma [42], urothelial carcinoma [43], multiple myeloma [44], and colorectal cancer [12] and predicts rapid recurrence after surgery of endometrial cancer [45] and in pancreatic cancer patients undergoing gemcitabine-adjuvant chemotherapy [46]. ANXA2 down-regulation is associated with recurrence and poor prognosis of prostate cancer [47] and oral squamous cell carcinoma [48]. However, although dysregulation of ANXA2 expression predicts adverse prognosis of patients with a wide variety of malignant tumors according to a systematic review and meta-analysis [49], there is increasing evidence that ANXA2 is a differential diagnostic tissue and serum marker for HCC [13]; the relationship between ANXA2 expression and prognosis of HCC patients has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma

Zhang

Yao

et al. 2015

Tumor Biol.

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Hepatic annexin A2 (ANXA2) orchestrates multiple biologic processes and clinical symptoms and plays a key role in development, metastasis, and drug resistance of lethal hepatocellular carcinoma (HCC). However, the prognostic significance of ANXA2 for HCC has not been elucidated up to now. In this study, ANXA2 was frequently found to be up-regulated in HCC tissues compared with benign liver disease (BLD) tissues, which was consistent with the results in serum samples and tissue specimens of patients with HCC. Furthermore, ANXA2 expression was significantly correlated with differentiated degree, intrahepatic metastasis, portal vein thrombus, and tumor node metastasis (TNM) staging. More importantly, increased ANXA2 level was first confirmed to be closely associated with shortened overall survival of HCC (χ (2) = 12.872, P = 0.005) and identified as an independent prognostic factor (hazard ratio 1.338, 95 % confidence interval (CI) 1.013 ~ 1.766, P = 0.040), suggesting that ANXA2 up-regulation might represent an acquired metastasis phenotype of HCC, help to screen out high-risk population for HCC, or more effectively treat a subset of postsurgical HCC patients positive for ANXA2.

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Section: Discussionmentioning

confidence: 99%

Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma

Zhang

Yao

et al. 2015

Tumor Biol.

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“…In some other malignancies, such as laryngeal and squamous cell carcinoma (46), head and neck dysplasia (47), and osteosarcoma (48), ANXA2 is downregulated and its absence is correlated with poorly-differentiated tumors and with poor prognosis. When up-regulated, ANXA2 functions as a co-receptor for plasminogen, tPA and pro-cathepsin B and promotes the conversion of plasminogen into plasmin, which is required for invasion, metastasis and angiogenesis (10, 41).…”

Section: Discussionmentioning

confidence: 99%

ERG Oncoprotein Inhibits ANXA2 Expression and Function in Prostate Cancer

Griner

Young

Chaudhary

et al. 2015

Molecular Cancer Research

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Overexpression of ERG in the prostate epithelium, due to chromosomal translocations, contributes to prostate tumorigenesis. Here, analysis of ERG siRNA-treated prostate cells harboring the endogenous TMPRSS2-ERG fusion revealed an inverse relationship between ERG and Annexin A2 (ANXA2) expression at both the RNA and protein level. ANXA2, a Ca2+-dependent and phospholipid–binding protein, is involved in various cellular functions, including maintenance of epithelial cell polarity. Mechanistic studies defined the prostate-specific transcription start site of ANXA2 and showed that the recruitment of ERG to the ANXA2 promoter is required for transcriptional repression by ERG. Knockdown of ERG enhanced the apical localization of ANXA2, the bundling of actin filaments at cell-cell junctions and formation of a polarized epithelial phenotype. ERG overexpression disrupted ANXA2 mediated cell polarity and promoted epithelial mesenchymal transition (EMT) by inhibiting CDC42 and RHOA, and by activating cofilin. Immunohistochemistry (IHC), demonstrated a reciprocal relationship of ANXA2 and ERG expression in a large fraction of primary prostate cancer clinical specimens. ANXA2 was absent or markedly reduced in ERG(+) tumors, which were mostly well-differentiated. ERG(−) tumors, meanwhile, expressed moderate to high levels of ANXA2, and were either poorly-differentiated or displayed subsets of poorly-differentiated cells. Taken together, the transcriptional repression of ANXA2 by ERG in prostate epithelial cells plays a critical role in abrogating differentiation, promoting EMT, and in the reciprocal correlation of ERG and ANXA2 expression observed in human prostate cancer. IMPLICATIONS ANXA2 is a new component of the ERG network with potential to enhance biological stratification and therapeutic targeting of ERG stratified prostate cancers.

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“…A2 and a related A2-binding “receptor” has been reported to promote myeloma cell adhesion and growth in the bone marrow [102]. On the other hand, A2 expression in oral squamous cell carcinoma [103] or sinonasal adenocarcinoma [104] was found to be inversely related to histopathologic grade. These studies suggest that expression levels of A2 may have prognostic value in malignancy, but would need to be validated for each specific tumor.…”

Section: Lessons From the Clinicmentioning

confidence: 99%

The Annexin A2/S100A10 System in Health and Disease: Emerging Paradigms

Hedhli

Falcone

Huang

et al. 2012

Journal of Biomedicine and Biotechnology

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Since its discovery as a src kinase substrate more than three decades ago, appreciation for the physiologic functions of annexin A2 and its associated proteins has increased dramatically. With its binding partner S100A10 (p11), A2 forms a cell surface complex that regulates generation of the primary fibrinolytic protease, plasmin, and is dynamically regulated in settings of hemostasis and thrombosis. In addition, the complex is transcriptionally upregulated in hypoxia and promotes pathologic neoangiogenesis in the tissues such as the retina. Dysregulation of both A2 and p11 has been reported in examples of rodent and human cancer. Intracellularly, A2 plays a critical role in endosomal repair in postarthroplastic osteolysis, and intracellular p11 regulates serotonin receptor activity in psychiatric mood disorders. In human studies, the A2 system contributes to the coagulopathy of acute promyelocytic leukemia, and is a target of high-titer autoantibodies in patients with antiphospholipid syndrome, cerebral thrombosis, and possibly preeclampsia. Polymorphisms in the human ANXA2 gene have been associated with stroke and avascular osteonecrosis of bone, two severe complications of sickle cell disease. Together, these new findings suggest that manipulation of the annexin A2/S100A10 system may offer promising new avenues for treatment of a spectrum of human disorders.

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Clinical significance of annexin A2 downregulation in oral squamous cell carcinoma

Cited by 25 publications

References 68 publications

Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma

Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma

ERG Oncoprotein Inhibits ANXA2 Expression and Function in Prostate Cancer

The Annexin A2/S100A10 System in Health and Disease: Emerging Paradigms

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