Annexin-A1 – A Blessing or a Curse in Cancer?

Foo, Sok Lin; Yap, Gracemary; Cui, Jianzhou; Lim, Lina H.K.

doi:10.1016/j.molmed.2019.02.004

Cited by 80 publications

(66 citation statements)

References 108 publications

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“…Annexin A1 (ANXA1), a member of calcium-dependent phospholipid-binding proteins, serves a role in regulating cell proliferation, apoptosis, phagocytosis and carcinogenesis (7,8). Studies have demonstrated that ANXA1 expression is different in various types of tumor tissue (8,9). For example, ANXA1 expression is upregulated in liver, colorectal and pancreatic cancer, but downregulated in prostate, esophageal and cervical cancer (9).…”

Section: Introductionmentioning

confidence: 99%

Annexin A1 is a potential biomarker of bone metastasis in small cell lung cancer

Chen

Min²,

et al. 2020

Oncol Lett

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Small cell lung cancer (SCLC) is a subtype of lung cancer with a poor prognosis, with bone metastasis being one of the main causes of treatment failure. Therefore, investigating new biomarkers associated with bone metastasis may result in positive treatment outcomes. The present study detected the expression levels of annexin A1 (ANXA1) in the serum of 82 patients with SCLC using ELISA. ANXA1 expression in patients with SCLC with bone metastasis was significantly higher compared with that in patients without bone metastasis. Receiver operating characteristic analysis revealed that ANXA1 expression was significant in the diagnosis of bone metastasis in SCLC. ANXA1 was inhibited in SBC-5 cells and overexpressed in SBC-3 cells. Results revealed that ANXA1 was able to enhance SCLC cell proliferation, invasion, migration and bone adhesion in vitro . In vivo xenograft bone metastasis assays indicated that ANXA1 had the potential to promote the bone-metastasis ability of SCLC cells in NOD/SCID mice. Furthermore, ANXA1 increased parathyroid hormone-related protein secretion and enhanced Smad2 phosphorylation following TGF-β treatment in SCLC cells. Overall, ANXA1 may be involved in the pathogenesis of bone metastasis in SCLC and may be a potential biomarker for the diagnosis of SCLC.

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Section: Introductionmentioning

confidence: 99%

Annexin A1 is a potential biomarker of bone metastasis in small cell lung cancer

Chen

Min²,

et al. 2020

Oncol Lett

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“…AnxA1 is known to play a role in tumor cell proliferation [22,23] and has been shown to be involved in metastatic behavior in cancer cells, including invasion, migration, and epithelial-mesenchymal transition [24][25][26][27][28][29][30][31]. Immunohistochemistry (IHC) studies have demonstrated that anxA1 is upregulated in several tumor types, including melanoma [32], hepatocellular carcinoma [33], gastric cancer [34][35][36], and non-small-cell lung carcinoma (NSCLC) [37][38][39][40], and is downregulated in prostate cancer [41,42] and many head and neck cancers [43][44][45][46]. It has been reported that the expression of anxA1 was significantly associated with the pathological grade of lung cancer while the upregulation of anxA1 correlated with decreased survival [47].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of annexin A1 protein expression in the intratumoral vasculature of human non–small-cell lung carcinoma and rodent tumor models

et al. 2020

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Annexin A1 (anxA1) is an immunomodulatory protein that has been proposed as a tumor vascular target for antitumor biologic agents, yet to date the vascular expression of anxA1 in specific tumor indications has not been systematically assessed. Attempts to evaluate vascular anxA1 expression by immunohistochemistry are complicated by a lack of available antibodies that are both specific for anxA1 and bind the N-terminal-truncated form of anxA1 that has previously been identified in tumor vasculature. To study the vascular expression pattern of anxA1 in non-small-cell lung carcinoma (NSCLC), we isolated an antibody capable of binding N-terminal-truncated anxA1 27-346 and employed it in immunohistochemical studies of human lung specimens. Lung tumor specimens evaluated with this antibody revealed vascular (endothelial) anxA1 expression in five of eight tumor samples studied, but no vascular anxA1 expression was observed in normal lung tissue. Tumor microarray analysis further demonstrated positive vascular staining for anxA1 in 30 of 80 NSCLC samples, and positive staining of neoplastic cells was observed in 54 of 80 samples. No correlation was observed between vascular and parenchymal anxA1 expression. Two rodent tumor models, B16-F10 and Py230, were determined to have upregulated anxA1 expression in the intratumoral vasculature. These data validate anxA1 as a potential vascular anti-tumor target in a subset of human lung tumors and identify rodent models which demonstrate anxA1 expression in tumor vasculature.

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“…Dysregulation of apoptosis is also regarded as a hallmark of PCa [27][28][29]. Hence, restore the normal apoptotic cell death in PCa is a critical treatment strategy [30][31][32], such as androgen deprivation therapy [33]. However, after current ADT therapy mostly advanced PCa development to castration-resistant prostate cancer (CRPC), force physicians to find different strategies according to novel AR-related mechanisms [34].…”

Section: Discussionmentioning

confidence: 99%

Phosphoribosyl pyrophosphate synthetases 2 knockdown inhibits prostate cancer progression by suppressing cell cycle and inducing cell apoptosis

Qiao¹,

Tan²,

Lv³

et al. 2020

J. Cancer

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Phosphoribosyl pyrophosphate synthetases 2 (PRPS2) protein function as nucleotide synthesis enzyme that plays vital roles in cancer biology. However, the expression profile and function of PRPS2 in prostate cancer (PCa) remain to be identified. Here we investigated the expression of PRPS2 protein in human PCa and paired normal tissues by immunohistochemistry, meanwhile the regulatory effects on cell proliferation, apoptosis and growth of xenograft tumors in nude mice were evaluated in PCa cells with PRPS2 depletion. Moreover, the signaling pathways were also explored by western blot analysis and quantitative polymerase chain reaction assays. We found that PRPS2 was dramatically upregulated in prostate adenocarcinoma tissues in comparison with normal tissues, and that increased PRPS2 was linked intimately to advanced clinical stage and pT status. Functional experiments showed that knockdown of PRPS2 significantly suppressed cell growth both in vitro and in vivo. In addition, depletion of PRPS2 induced G1 phase cell cycle arrest and elevated cell apoptosis. Silencing of PRPS2 resulted in the decreased expression of Bcl-2 and cyclinD1 and increased levels of Bax, cleavage of caspases-3, caspases-9 and PARP. Furthermore, we also detected PRPS2 expression was significantly induced after DHT treatment, which implied the important role of PRPS2 in oncogenesis of PCa. Taken together, our findings elucidated that PRPS2 may be a potential novel candidate for PCa therapy.

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Annexin-A1 – A Blessing or a Curse in Cancer?

Cited by 80 publications

References 108 publications

Annexin A1 is a potential biomarker of bone metastasis in small cell lung cancer

Annexin A1 is a potential biomarker of bone metastasis in small cell lung cancer

Upregulation of annexin A1 protein expression in the intratumoral vasculature of human non–small-cell lung carcinoma and rodent tumor models

Phosphoribosyl pyrophosphate synthetases 2 knockdown inhibits prostate cancer progression by suppressing cell cycle and inducing cell apoptosis

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