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Stem Cell Reviews and Reports Oct 2020Survivin is one of the rare proteins that is differentially expressed in normal and cancer cells and is directly or indirectly involved in numerous pathways required for... (Review)
Review
Survivin is one of the rare proteins that is differentially expressed in normal and cancer cells and is directly or indirectly involved in numerous pathways required for tumor maintenance. It is expressed in almost all cancers and its expression has been detected at early stages of cancer. These traits make survivin an exceptionally attractive target for cancer therapeutics. Even with these promising features to be an oncotherapeutic target, there has been limited success in the clinical trials targeting survivin. Only recently it has emerged that survivin was not being specifically targeted which could have resulted in the negative clinical outcome. Also, focus of research has now shifted from survivin expression in the overall heterogeneous tumor cell populations to survivin expression in cancer stem cells as these cells have proved to be the major drivers of tumors. Therefore, in this review we have analyzed the expression of survivin in normal and cancer cells with a particular focus on its expression in cancer stem cell compartment. We have discussed the major signaling pathways involved in regulation of survivin. We have explored the current development status of various types of interventions for inhibition of survivin. Furthermore, we have discussed the challenges involving the development of potent and specific survivin inhibitors for cancer therapeutics. Finally we have given insights for some of the promising future anticancer treatments.
Topics: Drug Development; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Neoplastic Stem Cells; Stem Cells; Survivin
PubMed: 32691369
DOI: 10.1007/s12015-020-09995-4 -
Bioscience Reports Jan 2021Survivin is an inhibitor of apoptosis as well as a promoter of cell proliferation. Fibulin-3 is a matrix glycoprotein that displays potential for tumor suppression or...
Survivin is an inhibitor of apoptosis as well as a promoter of cell proliferation. Fibulin-3 is a matrix glycoprotein that displays potential for tumor suppression or propagation. The present study aimed to validate the expression levels of survivin and fibulin-3 in benign and malignant respiratory diseases. This case-control study included 219 patients categorized into five groups. Group A included 63 patients with lung cancer, group B included 63 patients with various benign lung diseases, group D included 45 patients with malignant pleural mesothelioma (MPM), and group E included 48 patients with various benign pleural diseases. Group C included 60 healthy individuals (control group). Serum survivin and fibulin-3 levels were measured by ELISA, whereas their nuclear expressions in the lung and pleura were assessed via Western blot analysis. The results showed significantly higher survivin serum levels and significantly lower fibulin-3 levels in group A compared with in group B and controls (P<0.001). There were significantly higher serum levels of survivin and fibulin-3 in group D compared with in group E and controls (P<0.001), consistent with observed nuclear survivin and fibulin-3 expression levels. Fibulin-3 was determined to have higher value than survivin in discriminating lung cancer from MPM (P<0.05). Survivin and fibulin-3 could be useful diagnostic markers for lung and pleural cancers, and fibulin-3 expression was particularly useful in differentiating lung cancer from MPM.
Topics: Biomarkers; Blotting, Western; Case-Control Studies; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Female; Humans; Male; Mesothelioma, Malignant; Middle Aged; Pleural Diseases; Survivin
PubMed: 33226065
DOI: 10.1042/BSR20203097 -
PloS One 2013Emerging evidence showed that common functional -31G>C polymorphism (rs9904341 G>C) in the promoter region of the survivin gene is involved in the regulation of survivin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Emerging evidence showed that common functional -31G>C polymorphism (rs9904341 G>C) in the promoter region of the survivin gene is involved in the regulation of survivin expression, thus increasing an individual's susceptibility to gastrointestinal tract (GIT) cancer; but individually published results are inconclusive. The aim of this systematic review and meta-analysis was to derive a more precise estimation of the association between survivin -31G>C polymorphism and GIT cancer risk.
METHODS
A literature search of PubMed, Embase, Web of Science and CBM databases was conducted from inception through July 1st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.
RESULTS
Nine case-control studies were included with a total of 2,231 GIT cancer cases and 2,287 healthy controls. The results indicated that survivin -31G>C polymorphism was associated with increased risk of GIT cancer. In the stratified analysis by cancer types, significant associations were observed between survivin -31G>C polymorphism and increased risk of colorectal and gastric cancers. However, the lack of association of survivin -31G>C polymorphism with esophageal cancer risk may be due to a lack of a sufficient number of eligible studies and the influence of different genetic and environmental factors.
CONCLUSION
Results from the current meta-analysis suggests that survivin -31G>C polymorphism might increase the risk of GIT cancer, especially among gastric and colorectal cancers.
Topics: Case-Control Studies; Gastrointestinal Neoplasms; Genetic Predisposition to Disease; Humans; Inhibitor of Apoptosis Proteins; Polymorphism, Genetic; Promoter Regions, Genetic; Risk; Risk Factors; Survivin
PubMed: 23405077
DOI: 10.1371/journal.pone.0054081 -
International Journal of Cancer Sep 2007Although disease management of head and neck squamous cell carcinomas (HNSCC) has improved significantly, therapy resistance leading to tumor recurrence still... (Review)
Review
Although disease management of head and neck squamous cell carcinomas (HNSCC) has improved significantly, therapy resistance leading to tumor recurrence still counteracts improvement of long-term survival. Consequently, identification of molecular markers that signal increased risk of treatment failure or, which can be exploited by targeted therapy, is urgently needed. Survivin is strongly expressed in HNSCC, and its proposed dual role as an apoptosis inhibitor and a mitotic effector positioned survivin in the front line of cancer research. Notably, survivin is detected as a cytoplasmic and as a nuclear protein in HNSCC patients, which stimulated numerous studies to investigate and to speculate on the functional and prognostic significance of its dynamic localization. This review focuses on our current understanding of the molecular mechanisms regulating survivin's intracellular localization and discusses its potential prognostic and therapeutic relevance for head and neck cancer.
Topics: Animals; Biomarkers, Tumor; Head and Neck Neoplasms; Humans; Inhibitor of Apoptosis Proteins; Microtubule-Associated Proteins; Neoplasm Proteins; Prognosis; Survivin
PubMed: 17617794
DOI: 10.1002/ijc.22941 -
Histology and Histopathology Jan 2015The tumor microenvironment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Factors released by... (Review)
Review
The tumor microenvironment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Factors released by tumor cells themselves contribute in creating an environment mostly favorable but sometimes detrimental to the tumor. Survivin, one of the key members of the inhibitor of apoptosis (IAP) family of proteins, has been shown in the cytoplasm, mitochondria, nucleus, and most recently in the extracellular space, transported via small membrane bound vesicles called exosomes. Exosomes are secreted from hematopoietic, non-hematopoietic, tumor, and non-tumor cells, shuttling essential molecules such as proteins, RNAs, and microRNAs, all believed to be important for cell-cell and cell-extracellular communication. In this review, we discuss exosomal Survivin and its role in modifying the tumor microenvironment.
Topics: Exosomes; Humans; Inhibitor of Apoptosis Proteins; Neoplasms; Survivin; Tumor Microenvironment
PubMed: 25020159
DOI: 10.14670/HH-30.43 -
British Journal of Cancer Jan 2005Survivin, a unique member of the inhibitor of apoptosis (IAP) protein family, is highly expressed in cancer but is undetectable in nonproliferating normal adult tissues,... (Review)
Review
Survivin, a unique member of the inhibitor of apoptosis (IAP) protein family, is highly expressed in cancer but is undetectable in nonproliferating normal adult tissues, suggesting a potential role in tumorigenesis. Differential splicing of survivin pre-mRNA results in three new survivin variants, survivin-DeltaEx3, survivin-2B, and survivin-3B. Loss of survivin-2B expression was found in the later stage of cancer development, while survivin and survivin-DeltaEx3 are not, suggesting a differential role of them in tumour development. In this minireview, the author intends to summarise and discuss the current data relevant to the role of survivin and its splicing variants in tumorigenesis, which may facilitate further investigation in this interesting area.
Topics: Animals; Apoptosis; Humans; Inhibitor of Apoptosis Proteins; Microtubule-Associated Proteins; Neoplasm Proteins; Neoplasms; Recombination, Genetic; Survivin
PubMed: 15611788
DOI: 10.1038/sj.bjc.6602340 -
European Review For Medical and... Jun 2018To investigate the expressions of HIF-1α, surviving, and VEGF in patients with hepatocarcinoma as well as the correlation analysis among them.
OBJECTIVE
To investigate the expressions of HIF-1α, surviving, and VEGF in patients with hepatocarcinoma as well as the correlation analysis among them.
PATIENTS AND METHODS
65 patients, who were admitted to our hospital and diagnosed as hepatocarcinoma from January 2014 to October 2015, were selected as hepatocarcinoma group, while 50 healthy cases that do not have hepatocarcinoma were selected as normal control group. The expression levels of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group and normal liver tissues of control group were detected by immunohistochemical (SP) staining method; then, the correlation among them was explored. The expression levels of HIF-1α, surviving, and VEGF protein in hepatocarcinoma tissues and corresponding normal tissues were detected by Western blot.
RESULTS
The positive expression rate of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group was respectively 46.2%, 55.4%, and 61.5%, significantly higher than that in cancer adjacent normal liver tissues of control group which was 2%, 2%, and 2%, and the differences were statistically significant (p<0.05). The expressions of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of patients with hepatocarcinoma were correlated with clinical stage, tumor differentiation degree and extrahepatic metastasis (p<0.05), but were not related to gender and tumor size (p>0.05). By Spearman rank correlation analysis, it could be seen that HIF-1α expression was positively correlated with VEGF protein expression in hepatocarcinoma tissues (r=0.683, p<0.05). Survivin expression was positively correlated with VEGF protein expression (r=0.717, p<0.05). There was no significant correlation between HIF-1α expression and survivin expression (p>0.05). The relative quantitative value of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group was respectively 3.04±0.23, 2.26±0.31, and 2.57±0.36, significantly higher than that in cancer adjacent liver tissues of control group which was 1.07±0.17, 1.31±0.27, and 1.42±0.43, and the differences were statistically significant (p<0.05). From Western blot electrophoresis scanning, it could be seen that the expressions of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues were higher than those in cancer adjacent normal liver tissues.
CONCLUSIONS
The expressions of HIF-1α, surviving, and VEGF played important roles in the occurrence, invasion, and metastasis of hepatocarcinoma. In hepatocarcinoma tissues, HIF-1α, and survivin protein expression was positively correlated with VEGF expression, but survivin protein was not related to HIF-1α expression, which indicated that HIF-1α and survivin may inhibit the apoptosis of hepatocarcinoma cells and promote tumor angiogenesis by up-regulating the expression of VEGF protein, thus accelerating the occurrence and development of hepatocarcinoma.
Topics: Adult; Aged; Carcinoma, Hepatocellular; Case-Control Studies; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Liver Neoplasms; Male; Middle Aged; Neovascularization, Pathologic; Survivin; Up-Regulation; Vascular Endothelial Growth Factor A
PubMed: 29917189
DOI: 10.26355/eurrev_201806_15159 -
Journal of Experimental & Clinical... Aug 2019Survivin (also named BIRC5) is a well-known cancer therapeutic target. Since its discovery more than two decades ago, the use of survivin as a target for cancer... (Review)
Review
Survivin (also named BIRC5) is a well-known cancer therapeutic target. Since its discovery more than two decades ago, the use of survivin as a target for cancer therapeutics has remained a central goal of survivin studies in the cancer field. Many studies have provided intriguing insight into survivin's functional role in cancers, thus providing promise for survivin as a cancer therapeutic target. Despite this, moving survivin-targeting agents into and through the clinic remains a challenge. In order to address this challenge, we may need to rethink current strategies in order to develop a new mindset for targeting survivin. In this Review, we will first summarize the current survivin mechanistic studies, and then review the status of survivin cancer therapeutics, which is classified into five categories: (i) survivin-partner protein interaction inhibitors, (ii) survivin homodimerization inhibitors, (iii) survivin gene transcription inhibitors, (iv) survivin mRNA inhibitors and (v) survivin immunotherapy. We will then provide our opinions on cancer therapeutics using survivin as a target, with the goal of stimulating discussion that might facilitate translational research for discovering improved strategies and/or more effective anticancer agents that target survivin for cancer therapy.
Topics: Antineoplastic Agents; Humans; Molecular Targeted Therapy; Neoplasms; Prognosis; Survivin
PubMed: 31439015
DOI: 10.1186/s13046-019-1362-1 -
Veterinary Pathology Mar 2019Canine prostatic carcinoma is a relevant model for human prostatic carcinoma. Survivin is proposed as a biomarker of malignancy in human prostatic cancer. Sox9 is a stem...
Canine prostatic carcinoma is a relevant model for human prostatic carcinoma. Survivin is proposed as a biomarker of malignancy in human prostatic cancer. Sox9 is a stem cell marker required for prostate development and expressed in several adult tissues. The aims of the present study were to evaluate the patterns and expression levels of 2 putative stem cell markers, survivin and Sox9, in canine benign prostatic hyperplasia (BPH) and prostatic carcinoma to investigate their potential as stem cell markers. Immunohistochemistry with specific antibodies was performed on 3 samples of normal prostate gland, 18 samples of canine BPH, and 16 samples of prostatic carcinoma. The basal cell layer of normal and hyperplastic prostatic lobules had nuclear Sox9 immunolabeling and nuclear and rarely cytoplasmic survivin immunostaining, identifying them as potential stem cell markers. Significantly more frequent survivin and Sox9 expression (≥10% of nuclei) was observed in prostatic carcinoma as compared with BPH. The potential coexpression of survivin with Sox9, androgen receptor, and p63 was also investigated in selected BPH and prostatic carcinoma cases with immunofluorescence, and a partial colocalization was observed. Results indicate that Sox9 and survivin could be considered markers of stemness in canine prostate cells. Given its role in proliferation, cells in the basal cell layer with nuclear survivin expression are likely to be transit-amplifying cells that maintain some stem cell proprieties.
Topics: Animals; Biomarkers, Tumor; Dog Diseases; Dogs; Fluorescent Antibody Technique; Male; Prostate; Prostatic Neoplasms; SOX9 Transcription Factor; Stem Cells; Survivin
PubMed: 30131013
DOI: 10.1177/0300985818794161 -
International Journal of Biological... 2018CD44, also known as homing cell adhesion molecule is a multi-structural cell molecule involved in cell-cell and cell-extracellular matrix communications. CD44 regulates... (Review)
Review
CD44, also known as homing cell adhesion molecule is a multi-structural cell molecule involved in cell-cell and cell-extracellular matrix communications. CD44 regulates a number of central signaling pathways, including PI3K/AKT, Rho GTPases and the Ras-MAPK pathways, but also acts as a growth/arrest sensor, and inhibitor of angiogenesis and invasion, in response to signals from the microenvironment. The function of CD44 has been very controversial since it acts as both, a suppressor and a promoter of tumor growth and progression. To address this discrepancy, we have previously established CD44-inducible system both and . Next, using microarray analysis, we have identified and validated Survivin, Cortactin and TGF-β2 as novel CD44-downstream target genes, and characterized their signaling pathways underpinning CD44-promoted breast cancer (BC) cell invasion. This report aims to update the literature by adding and discussing the impact of these novel three signaling pathways to better understand the CD44-signaling pathways involved in BC tumor cell invasion.
Topics: Breast Neoplasms; Cortactin; Female; Humans; Hyaluronan Receptors; Signal Transduction; Survivin; rho GTP-Binding Proteins
PubMed: 30443182
DOI: 10.7150/ijbs.23586