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Journal of Cell Science Apr 2019Survivin (also known as BIRC5) is an evolutionarily conserved eukaryotic protein that is essential for cell division and can inhibit cell death. Normally it is only... (Review)
Review
Survivin (also known as BIRC5) is an evolutionarily conserved eukaryotic protein that is essential for cell division and can inhibit cell death. Normally it is only expressed in actively proliferating cells, but is upregulated in most, if not all cancers; consequently, it has received significant attention as a potential oncotherapeutic target. In this Cell Science at a Glance article and accompanying poster, we summarise our knowledge of survivin 21 years on from its initial discovery. We describe the structure, expression and function of survivin, highlight its interactome and conclude by describing anti-survivin strategies being trialled.
Topics: Apoptosis; Humans; Mitosis; Molecular Targeted Therapy; Neoplasms; Survivin
PubMed: 30948431
DOI: 10.1242/jcs.223826 -
Genetic Testing and Molecular Biomarkers Sep 2022Breast cancer is the most frequently diagnosed cancer in women and ranks second among causes for cancer-related death in women. Gene technology has led to the... (Review)
Review
Breast cancer is the most frequently diagnosed cancer in women and ranks second among causes for cancer-related death in women. Gene technology has led to the recognition that breast cancer is a heterogeneous disease composed of different biological subtypes, and genetic profiling enables the response to chemotherapy to be predicted. This fact emphasizes the importance of selecting sensitive diagnostic and prognostic markers in the early disease stage and more efficient targeted treatments for this disease. One such prognostic marker appears to be survivin. Many studies have shown that survivin is strongly expressed in different types of cancers. Its overexpression has been demonstrated in breast cancer, and high activity of the survivin gene has been associated with a poor prognosis and worse survival rates.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Inhibitor of Apoptosis Proteins; Survivin
PubMed: 36166738
DOI: 10.1089/gtmb.2021.0286 -
European Journal of Cancer Prevention :... Jul 2019Survivin is one of the most cancer-specific proteins overexpressed in almost all malignancies, but is nearly undetectable in most normal tissues in adults. Functionally,... (Review)
Review
Survivin is one of the most cancer-specific proteins overexpressed in almost all malignancies, but is nearly undetectable in most normal tissues in adults. Functionally, as a member of the inhibitor of apoptosis family, survivin has been shown to inhibit apoptosis and increase proliferation. The antiapoptotic function of survivin seems to be related to its ability to inhibit caspases directly or indirectly. Furthermore, the role of survivin in cell cycle division control is related to its role in the chromosomal passenger complex. Consistent with its determining role in these processes, survivin plays a crucial role in cancer progression and cancer cell resistance to anticancer drugs and ionizing radiation. On the basis of these findings, recently survivin has been investigated intensively as an ideal tumor biomarker. Thus, multiple molecular approaches such as use of the RNA interfering technique, antisense oligonucleotides, ribozyme, and small molecule inhibitors have been used to downregulate survivin regulation and inhibit its biological function consequently. In this review, all these approaches are explained and other compounds that induced apoptosis in different cell lines through survivin inhibition are also reported.
Topics: Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Cell Line, Tumor; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Disease Progression; Down-Regulation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Neoplasms; Oligonucleotides, Antisense; Prognosis; RNA Interference; RNA, Catalytic; Radiation Tolerance; Survivin; Treatment Outcome; Xenograft Model Antitumor Assays
PubMed: 29847456
DOI: 10.1097/CEJ.0000000000000453 -
Immunology Letters Jan 2018Autoimmunity is a status that immune mechanisms react against self-structure. The immune mechanisms, including cellular and molecular elements have been developed to... (Review)
Review
Autoimmunity is a status that immune mechanisms react against self-structure. The immune mechanisms, including cellular and molecular elements have been developed to immune body against foreign invades. Multiple factors such as genetic and epigenetic background, hormonal status, microbiome, and other factors can cause launching the autoreactive responses, in which the immune tolerance breaks and immune mechanisms are against self-antigens. Apoptosis is one of the important mechanisms in maintaining the tolerance and eliminating the autoreactive lymphocyte clones. Due to survivin roles in apoptosis and proliferation, numerous researches have been paying attention to survivin expression and function in autoreactive lymphocytes and tissue cells, playing important roles in the pathogenesis of autoimmune diseases. New line of evidence has been supporting the role of survivin dysfunction or aberrant expression in deriving autoreactive lymphocytes or some important immune tissues, which may underpin the autoimmune conditions such as Lichen planus (LP), Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), Myasthenia gravis (MG), Multiple sclerosis (MS), Systemic sclerosis (SSc), Psoriasis, and Inflammatory bowel disease (IBD). Hence, the purpose of the current paper was to review the survivin role in the etiology and pathogenesis of abovementioned autoimmune diseases.
Topics: Animals; Apoptosis; Autoimmune Diseases; Autoimmunity; Humans; Immune Tolerance; Inhibitor of Apoptosis Proteins; Survivin
PubMed: 29155234
DOI: 10.1016/j.imlet.2017.11.004 -
Journal of Cellular Physiology Dec 2019Rheumatoid arthritis (RA) is an autoimmune disease, pathologically characterized by lymphocyte infiltration of the synovial membrane that leads to chronic inflammation... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disease, pathologically characterized by lymphocyte infiltration of the synovial membrane that leads to chronic inflammation and progressive joint damage. RA develops as a result of increased cell infiltration and cell proliferation as well as impaired cell death. Activated cells in joints including lymphocytes and fibroblast-like synoviocytes (FLS) survive for a long time as a consequence of compromised apoptosis, but the mechanism underlying cell survival in synovium remains to be firmly established. Inhibition of apoptosis by survivin, as a critical antiapoptotic protein, contributes to both the persistence of autoreactive T lymphocytes and tumor-like phenotype of FLS in RA. In addition to the antiapoptotic role, survivin also has prognostic relevance in RA prodromal phase. Hence, this review provides an overview of the current knowledge regarding the involvement of survivin protein in the pathogenesis of RA.
Topics: Animals; Apoptosis; Arthritis, Rheumatoid; Cell Proliferation; Humans; Inflammation; Survivin; Synovial Membrane; Synoviocytes
PubMed: 31062383
DOI: 10.1002/jcp.28784 -
Pathology, Research and Practice Apr 2019Thyroid cancer (TC) is known as the most prevalent form of endocrine malignancy. With regard to high heterogeneity of the nodules, problem of discriminating between... (Review)
Review
Thyroid cancer (TC) is known as the most prevalent form of endocrine malignancy. With regard to high heterogeneity of the nodules, problem of discriminating between benign and malignant ones in terms of pathological characteristics, as well as lack of appropriate molecular markers; significant efforts are being made to identify molecular markers that able to detect tumorous lesions. Survivin, the newest member of the family of proteins inhibiting cell apoptosis, has been recently considered as a novel molecule marker for cancer. Studies on TC have also demonstrated distinctive expression of survivin and its splice variants in cancer cells compared to normal ones. Therefore, detection of survivin expression and its new splice variants can be utilized to identify tumor nodules and distinguish them from non-cancerous ones, along with other routine laboratory methods.
Topics: Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Prognosis; Survivin; Thyroid Neoplasms
PubMed: 30683476
DOI: 10.1016/j.prp.2019.01.025 -
Frontiers in Immunology 2022It has been well established that the etiopathogenesis of diverse autoimmune diseases is rooted in the autoreactive immune cells' excessively proliferative state and... (Review)
Review
It has been well established that the etiopathogenesis of diverse autoimmune diseases is rooted in the autoreactive immune cells' excessively proliferative state and impaired apoptotic machinery. Survivin is an anti-apoptotic and mitotic factor that has sparked a considerable research interest in this field. Survivin overexpression has been shown to contribute significantly to the development of autoimmune diseases autoreactive immune cell overproliferation and apoptotic dysregulation. Several microRNAs (miRNAs/miRs) have been discovered to be involved in survivin regulation, rendering the survivin-miRNA axis a perspective target for autoimmune disease therapy. In this review, we discuss the role of survivin as an immune regulator and a highly implicated protein in the pathogenesis of autoimmune diseases, the significance of survivin-targeting miRNAs in autoimmunity, and the feasibility of targeting the survivin-miRNA axis as a promising therapeutic option for autoimmune diseases.
Topics: Autoimmune Diseases; Autoimmunity; Humans; MicroRNAs; Survivin
PubMed: 35309327
DOI: 10.3389/fimmu.2022.839945 -
Medicinal Research Reviews May 2019Survivin is a small protein that belongs to the inhibitor of apoptosis protein family. It is abundantly expressed in tumors compared with adult differentiated tissues,... (Review)
Review
Survivin is a small protein that belongs to the inhibitor of apoptosis protein family. It is abundantly expressed in tumors compared with adult differentiated tissues, being associated with poor prognosis in many human neoplasms. This apoptotic inhibitor has a relevant role in both the promotion of cancer cell survival and in the inhibition of cell death. Consequently, aberrant survivin expression stimulates tumor progression and confers resistance to several therapeutic strategies in a variety of tumors. In fact, efficient survivin downregulation or inhibition results in spontaneous apoptosis or sensitization to chemotherapy and radiotherapy. Therefore, all these features make survivin an attractive therapeutic target to treat cancer. Currently, there are several survivin inhibitors under clinical evaluation, although more specific and efficient survivin inhibitors are being developed. Moreover, novel combination regimens targeting survivin together with other therapeutic approaches are currently being designed and assessed. In this review, recent progress in the therapeutic options targeting survivin for cancer treatment is analyzed. Direct survivin inhibitors and their current development status are explored. Besides, the major signaling pathways implicated in survivin regulation are described and different therapeutic approaches involving survivin indirect inhibition are evaluated. Finally, promising novel inhibitors under preclinical or clinical evaluation as well as challenges of developing survivin inhibitors as a new therapy for cancer treatment are discussed.
Topics: Antineoplastic Agents; Cell Differentiation; Humans; Molecular Targeted Therapy; Neoplasms; Signal Transduction; Survivin
PubMed: 30421440
DOI: 10.1002/med.21547 -
Expert Opinion on Drug Discovery Jul 2022Due to its unique functional impact on multiple cancer cell circuits including proliferation, apoptosis, tumor dissemination, DNA damage repair, and immune response, the... (Review)
Review
INTRODUCTION
Due to its unique functional impact on multiple cancer cell circuits including proliferation, apoptosis, tumor dissemination, DNA damage repair, and immune response, the inhibitor of apoptosis protein (IAP) survivin has gained high interest as a molecular target and a multitude of therapeutics were developed to interfere with survivin expression and functionality. First clinical evaluations of these therapeutics, however, were disappointing highlighting the need to develop advanced delivery systems of survivin-targeting therapeutics.
AREAS COVERED
This review focuses on advancements in nanocarriers to molecularly target survivin in human malignancies. A plethora of nanoparticle platforms, including liposomes, polymeric systems, dendrimers, inorganic nanocarriers, RNA/DNA nanotechnology and exosomes, are discussed in the background of survivin-tailored RNA interference, small molecule inhibitors, dominant negative mutants or survivin vaccination or combined modality treatment with chemotherapeutic drugs and photo-dynamic/photothermal strategies.
EXPERT OPINION
Novel therapeutic approaches include the use of biocompatible nanoformulations carrying gene silencing or drug molecules to directly or indirectly target proteins, allow for a more precise and controlled delivery of survivin therapeutics. Moreover, surface modification of these nanocarriers may result in a tumor entity-specific delivery. Therefore, nanomedicine exploiting survivin-tailored strategies in a multimodal background is considered the way forward to enhance the development of future personalized medicine.
Topics: Drug Delivery Systems; Drug Discovery; Humans; Nanomedicine; Nanoparticles; Nanotechnology; Neoplasms; Survivin
PubMed: 35593177
DOI: 10.1080/17460441.2022.2077329 -
Blood Reviews Sep 2020Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the BCR-ABL oncoprotein, known to drive leukemogenesis by orchestrating multiple... (Review)
Review
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the BCR-ABL oncoprotein, known to drive leukemogenesis by orchestrating multiple signaling pathways ultimately involved in cell survival. Despite successful response rates of CML patients to tyrosine kinase inhibitors (TKIs), resistance eventually arises due to BCR-ABL-dependent and independent mechanisms. Survivin is an inhibitor of apoptosis protein acting in the interface between apoptosis deregulation and cell cycle progression. In CML, high levels of survivin have been associated with late stages of disease and therapy resistance. In this review, we provide an overview of important aspects concerning survivin subcellular localization and expression pattern in CML patients and cell lines. Moreover, we highlight the relevance of molecular networks involving survivin for disease progression and treatment resistance. Finally, we discuss the mechanisms accounting for survivin overexpression, as well as novel therapeutic interventions that have been designed to counteract survivin-associated malignancy in CML.
Topics: Animals; Antineoplastic Agents; Drug Resistance, Neoplasm; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Targeted Therapy; Protein Kinase Inhibitors; Survivin; Up-Regulation
PubMed: 32107072
DOI: 10.1016/j.blre.2020.100671