Expression of Stanniocalcin 2 in Breast Cancer and Its Clinical Significance

Jiang, Shanwen; Wang, Huaqiao; Yang, Tiecheng; Wang, Danwen; Yang, Lei; Xi, Yue; Kong, Fan-Zheng; Pan, Xuekai; Xu, Lihua; Mao, Feng; Su, Fei

doi:10.1007/s11596-019-2131-2

Cited by 14 publications

(13 citation statements)

References 20 publications

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“…It is upregulated in response to metabolic stresses, including hypoxia conditions (216), and forms part of the unfolded protein response (217). STC2 is also a tumor marker for several cancers as well as possibly involved in metastasis (218,219). Studies on STC2 have not been performed in reptiles, while expression patterns have been assessed in avian muscle and joint development (220).…”

Section: Discussionmentioning

confidence: 99%

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

et al. 2020

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Alligators are crocodilians and among few species that endured the Cretaceous-Paleogene extinction event. With long life spans, low metabolic rates, unusual immunological characteristics, including strong antibacterial and antiviral ability, and cancer resistance, crocodilians may hold information for molecular pathways underlying such physiological traits. Peptidylarginine deiminases (PADs) are a group of calcium-activated enzymes that cause posttranslational protein deimination/citrullination in a range of target proteins contributing to protein moonlighting functions in health and disease. PADs are phylogenetically conserved and are also a key regulator of extracellular vesicle (EV) release, a critical part of cellular communication. As little is known about PAD-mediated mechanisms in reptile immunology, this study was aimed at profiling EVs and protein deimination in Alligator mississippiensis. Alligator plasma EVs were found to be polydispersed in a 50-400-nm size range. Key immune, metabolic, and gene regulatory proteins were identified to be posttranslationally deiminated in plasma and plasma EVs, with some overlapping hits, while some were unique to either plasma or plasma EVs. In whole plasma, 112 target proteins were identified to be deiminated, while 77 proteins were found as deiminated protein hits in plasma EVs, whereof 31 were specific for EVs only, including proteins specific for gene regulatory functions (e.g., histones). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed KEGG pathways specific to deiminated proteins in whole plasma related to adipocytokine signaling, while KEGG pathways of deiminated proteins specific to EVs included ribosome, biosynthesis of amino acids, and glycolysis/gluconeogenesis pathways as well as core histones. This highlights roles for EV-mediated export of deiminated protein cargo with roles in metabolism and gene regulation, also related to cancer. The identification of posttranslational deimination and EV-mediated communication Criscitiello et al. Deimination and EV Signatures in Alligator in alligator plasma revealed here contributes to current understanding of protein moonlighting functions and EV-mediated communication in these ancient reptiles, providing novel insight into their unusual immune systems and physiological traits. In addition, our findings may shed light on pathways underlying cancer resistance, antibacterial and antiviral resistance, with translatable value to human pathologies.

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Section: Discussionmentioning

confidence: 99%

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

et al. 2020

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“…Interestingly, favorable effects of STC2 expression in breast cancer were reported in several studies [ 27–29 ]. STC2 expression was found to be higher in breast cancer patients with a predisposition toward late recurrence than in those with early metastases and relapses [ 30 ]. STC2 may serve as a survival factor for breast cancer cells, contributing to tumor dormancy [ 30 ].…”

Section: Stc2 In Breast Cancer and Gynecologic Cancersmentioning

confidence: 99%

“…STC2 expression was found to be higher in breast cancer patients with a predisposition toward late recurrence than in those with early metastases and relapses [ 30 ]. STC2 may serve as a survival factor for breast cancer cells, contributing to tumor dormancy [ 30 ]. Esseghir et al examined the expression of five genes including probes against thrombospondin 3, insulin-like growth factor binding protein 7, tumor rejection antigen 1, STC2, and netrin 4 in a tissue microarray containing 245 invasive breast tumors from women, which were found to be associated with a prolonged disease-free survival [ 31 ].…”

Section: Stc2 In Breast Cancer and Gynecologic Cancersmentioning

confidence: 99%

The significance of Stanniocalcin 2 in malignancies and mechanisms

Huang

et al. 2021

Bioengineered

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Human stanniocalcin 2 (STC2) is an ortholog of fish stanniocalcins (STCs) and is widely expressed in various organs and tissues. The gene is localized on chromosome 5q33 or 5q35. STC2 has been implicated in glucose homeostasis and phosphorus metabolism. It is also reported to be implicated in various malignancies. STC2 was found to be implicated in breast cancer and gynecologic cancers, suggesting hormone-specific or -dependent activities in these malignancies. Moreover, it was reported to be involved in gastrointestinal tumors, including esophageal, gastric, colorectal, and liver cancers, and respiratory cancers, including laryngeal and lung cancers. It also influenced renal carcinoma and prostate cancer. Notably, as a secreted phosphoprotein, STC2 was detectable in serum and possessed promising predictive value in several malignancies. This review aims to improve the understanding of the role of STC2 in patient diagnosis and prognosis, and tumor development and progression, as well as the mechanisms involved.

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“…Ectopic expression of STC2, an inhibitor of PAPP‐A, compromised breast cancer cell proliferation and motility [28]. However, high expression levels of STC2 were found in breast cancer tissues, especially in ER‐positive tissue [29]. As indicated earlier, several results conflict with the tumor‐promoting function of PAPP‐A.…”

Section: Discussionmentioning

confidence: 99%

PAPP‐A functions as a tumor suppressor and is downregulated in renal cell carcinoma

Wang

et al. 2021

FEBS Open Bio

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Pregnancy-associated plasma protein A (PAPP-A) is a proteolytic enzyme produced by the placenta. The expression and role of PAPP-A in renal cell carcinoma (RCC) remain elusive. The aim of this study was to investigate the role and the molecular mechanisms of PAPP-A in RCC. Initially, we evaluated the expression of PAPP-A in samples from patients with RCC and cell lines by quantitative PCR, western blot and immunohistochemical staining, and examined the role of PAPP-A in RCC cells by cell viability, colony formation and Transwell assays. Next, we investigated the molecular mechanisms regulating the tumor suppressor function of PAPP-A. Our results demonstrated that PAPP-A is expressed at low levels in RCC tissues and cells. Clinical data analysis revealed a significant correlation between PAPP-A expression and RCC-related death (P < 0.0115). Overexpression of PAPP-A inhibited viability, proliferation, migration and invasion of RCC cells. Furthermore, PAPP-A overexpression significantly increased phosphorylation of c-Jun N-terminal kinase and decreased the expression of cyclin D1, phosphorylated glycogen synthase kinase-3b and b-catenin. This study is the first to report that downregulation of PAPP-A is associated with poor prognosis in patients with RCC. In conclusion, PAPP-A may serve as a novel prognostic marker and potentially as a therapeutic target in patients with RCC.Renal cell carcinoma (RCC) comprises 2% to 3% of all adult malignancies; RCC has had a high incidence rate in recent years and accounts for~80% of primary renal malignancies [1]. Clear cell RCC (ccRCC) accounts for about 80% of RCCs and is the most aggressive subtype of RCC. Partial nephrectomy is the most effective therapeutic method for early and local RCC. However, up to 30% of patients experience development of metastases after surgery [2]. The mechanism of RCC formation and progression remains unclear. Therefore, exploring new targets associated with tumorigenesis may improve the potential therapeutic strategies and the therapeutic response of RCC.

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Expression of Stanniocalcin 2 in Breast Cancer and Its Clinical Significance

Cited by 14 publications

References 20 publications

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

The significance of Stanniocalcin 2 in malignancies and mechanisms

PAPP‐A functions as a tumor suppressor and is downregulated in renal cell carcinoma

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