S100A10 and Cancer Hallmarks: Structure, Functions, and its Emerging Role in Ovarian Cancer

Noye, Tannith M.; Lokman, Noor A.; Oehler, Martin K.; Ricciardelli, Carmela

doi:10.3390/ijms19124122

Cited by 34 publications

(28 citation statements)

References 114 publications

(173 reference statements)

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“…Although data from p11 KO-mice often supports findings that AnxA2/p11-dependent plasmin generation is involved in tumour progression [ 115 , 116 , 121 ], it should be noted that p11 has plenty of other tumourigenic functions that appear rather unrelated to AnxA2 [ 174 , 175 ]. It would also go beyond the scope of this review to discuss in detail cancer-related animal studies that identified upstream regulators of AnxA2 expression or activity [ 176 , 177 , 178 ].…”

Section: Anxa2mentioning

confidence: 85%

Annexin Animal Models—From Fundamental Principles to Translational Research

Grewal

Rentero

Enrich

et al. 2021

IJMS

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Routine manipulation of the mouse genome has become a landmark in biomedical research. Traits that are only associated with advanced developmental stages can now be investigated within a living organism, and the in vivo analysis of corresponding phenotypes and functions advances the translation into the clinical setting. The annexins, a family of closely related calcium (Ca2+)- and lipid-binding proteins, are found at various intra- and extracellular locations, and interact with a broad range of membrane lipids and proteins. Their impacts on cellular functions has been extensively assessed in vitro, yet annexin-deficient mouse models generally develop normally and do not display obvious phenotypes. Only in recent years, studies examining genetically modified annexin mouse models which were exposed to stress conditions mimicking human disease often revealed striking phenotypes. This review is the first comprehensive overview of annexin-related research using animal models and their exciting future use for relevant issues in biology and experimental medicine.

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Section: Anxa2mentioning

confidence: 85%

Annexin Animal Models—From Fundamental Principles to Translational Research

Grewal

Rentero

Enrich

et al. 2021

IJMS

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“…The ANXA2 subunit helps to stabilize and anchor S100A10 to the plasma membrane, and AIIt activates plasminogen via tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (uPA). This in turn increases the production of plasmin, leading to the activation of metalloproteinases (MMPs) and the degradation of extracellular matrix (ECM) proteins, thereby promoting tumor progression and chemoresistance [31, 32]. Liu et al found that ovarian cancer proliferation and invasion can be suppressed by inhibiting ANXA2 via β-catenin/EMT [33].…”

Section: Discussionmentioning

confidence: 99%

Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins

et al. 2019

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Background Annexins are involved in vesicle trafficking, cell proliferation and apoptosis, but their functional mechanisms in ovarian cancer remain unclear. In this study, we analyzed Annexins in ovarian cancer using different databases and selected Annexin A8 (ANXA8), which showed the greatest prognostic value, for subsequent validation in immunohistochemical (IHC) assays. Methods The mRNA expression levels, genetic variations, prognostic values and gene–gene interaction network of Annexins in ovarian cancer were analyzed using the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, Kaplan–Meier plotter and GeneMANIA database. ANXA8 was selected for analyzing the biological functions and pathways of its co-expressed genes, and its correlation with immune system responses via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and the TISIDB database, respectively. We validated the expression of ANXA8 in ovarian cancer via IHC assays and analyzed its correlation with clinicopathological parameters and prognosis. Results ANXA2/3/8/11 mRNA expression levels were significantly upregulated in ovarian cancer, and ANXA5/6/7 mRNA expression levels were significantly downregulated. Prognostic analysis suggested that significant correlations occurred between ANXA2/4/8/9 mRNA upregulation and poor overall survival, and between ANXA8/9/11 mRNA upregulation and poor progression-free survival in patients with ovarian serous tumors. Taken together, results suggested that ANXA8 was most closely associated with ovarian cancer tumorigenesis and progression. Further analyses indicated that ANXA8 may be involved in cell migration, cell adhesion, and vasculature development, as well as in the regulation of PI3K-Akt, focal adhesion, and proteoglycans. Additionally, ANXA8 expression was significantly correlated with lymphocytes and immunomodulators. The IHC results showed that ANXA8 expression was higher in the malignant tumor group than in the borderline and benign tumor groups and normal ovary group, and high ANXA8 expression was an independent risk factor for survival and prognosis of ovarian cancer patients ( P = 0.013). Conclusions Members of the Annexin family display varying degrees of abnormal expressions in ovarian cancer. ANXA8 was significantly highly expressed in ovarian cancer, and high ANXA8 expression was significantly correlated with poor prognosis. Therefore, ANXA8 is a high candidate as a novel biomarker and therapeutic target for ovarian cancer.

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“…Annexin A2 and S100A10 form a heterotetramer referred to as AIIt, which interacts with the tissue plasminogen activator (tPA). This leads to the production of plasmin, which results in ECM degradation, EMT, and angiogenesis [151,152]. In addition, S100A10 is able to promote MMPs, altogether provoking cell migration and invasion [153].…”

Section: S100 Proteins In Ovarian Cancermentioning

confidence: 99%

Friend or Foe: S100 Proteins in Cancer

Allgöwer

Kretz

Karstedt

et al. 2020

Cancers

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S100 proteins are widely expressed small molecular EF-hand calcium-binding proteins of vertebrates, which are involved in numerous cellular processes, such as Ca2+ homeostasis, proliferation, apoptosis, differentiation, and inflammation. Although the complex network of S100 signalling is by far not fully deciphered, several S100 family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer. The research of the past decades revealed that S100 proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma. Hence, S100 family members have also been shown to be promising diagnostic markers and possible novel targets for therapy. However, the current knowledge of S100 proteins is limited and more attention to this unique group of proteins is needed. Therefore, this review article summarises S100 proteins and their relation in different cancer types, while also providing an overview of novel therapeutic strategies for targeting S100 proteins for cancer treatment.

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S100A10 and Cancer Hallmarks: Structure, Functions, and its Emerging Role in Ovarian Cancer

Cited by 34 publications

References 114 publications

Annexin Animal Models—From Fundamental Principles to Translational Research

Annexin Animal Models—From Fundamental Principles to Translational Research

Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins

Friend or Foe: S100 Proteins in Cancer

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