Survivin, a cancer target with an emerging role in normal adult tissues

Fukuda, Seiji; Pelus, Louis M.

doi:10.1158/1535-7163.mct-05-0375

Cited by 432 publications

(386 citation statements)

References 136 publications

(145 reference statements)

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“…Furthermore, survivin has been also found in the nucleus and cytosol where the implication is that it has functions in mitosis regulation and apoptosis inhibition, respectively (Fortugno et al, 2002). Survivin is expressed in most common human cancers and although present during embryonic and foetal development, it is undetectable in a variety of adult tissues (Adida et al, 1998) and for this reason it is currently recognised as an important anticancer target (Fukuda and Pelus, 2006). For this purpose, multiple strategies have been successfully investigated, including the molecular antagonists such as antisense oligos, RNA inhibition, dominantnegative mutants, survivin-specific cytolytic T cells, a nonphosphorylatable survivin mutant Thr 34 -Ala (T34A), and most recently, binding interface mimetics (Olie et al, 2000;Andersen et al, 2001;Grossman et al, 2001;Kanwar et al, 2001;Mesri et al, 2001;Wall et al, 2003;Plescia et al, 2005).…”

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confidence: 99%

Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential

et al. 2009

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The tumour microenvironment is believed to be involved in development, growth, metastasis, and therapy resistance of many cancers. Here we show survivin, a member of the inhibitor of apoptosis protein (IAP) family, implicated in apoptosis inhibition and the regulation of mitosis in cancer cells, exists in a novel extracellular pool in tumour cells. Furthermore, we have constructed stable cell lines that provide the extracellular pool with either wild-type survivin (Surv-WT) or the previously described dominant-negative mutant survivin (Surv-T34A), which has proven pro-apoptotic effects in cancer cells but not in normal proliferating cells. Cancer cells grown in conditioned medium (CM) taken from Surv-WT cells absorbed survivin and experienced enhanced protection against genotoxic stresses. These cells also exhibited an increased replicative and metastatic potential, suggesting that survivin in the tumour microenvironment may be directly associated with malignant progression, further supporting survivin's function in tumourigenesis. Alternatively, cancer cells grown in CM taken from the Surv-T34A cells began to apoptose through a caspase-2-and caspase-9-dependent pathway that was further enhanced by the addition of other chemo-and radiotherapeutic modalities. Together our findings suggest a novel microenvironmental function for survivin in the control of cancer aggressiveness and spread, and should result in the genesis of additional cancer treatment modalities.

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confidence: 99%

Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential

et al. 2009

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“…Overexpression of survivin, a member of the IAP family of proteins, is attributed to the chemoresistance of tumor cells (Adida et al, 2000;Fukuda and Pelus, 2006;Ryan et al, 2009;Feng et al, 2013). On the contrary, different studies have shown that suppression of survivin expression can sensitize tumor cells to anti-cancer drugs (Zaffaroni et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike other IAP members, survivin is largely expressed in embryonic and fetal tissues as well as in many malignant cells, but not in normal adult tissues (Zaffaroni and Daidone, 2002;Coumar et al, 2013). Previous reports have demonstrated that the overexpression of survivin is correlated with tumor progression, poor prognosis and drug resistance in many cancers including AML (Adida et al, 2000;Fukuda and Pelus, 2006). Because of this overexpression in cancer, its important role in apoptosis as well as cell division, and its association with drug resistance, survivin has been considered as an attractive therapeutic target in malignancies (Ryan et al, 2009;Feng et al, 2013).…”

Section: Sirna-mediated Silencing Of Survivin Inhibits Proliferationmentioning

confidence: 99%

siRNA-mediated Silencing of Survivin Inhibits Proliferation and Enhances Etoposide Chemosensitivity in Acute Myeloid Leukemia Cells

Karami¹,

Baradaran²,

Esfahani³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Overexpression of survivin, a known inhibitor of apoptosis, is associated with tumor progression and drug resistance in numerous malignancies, including leukemias. The aim of this study was to investigate the effect of a specific survivin small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug etoposide. Materials and Methods: The cells were transfected with siRNAs using Lipofectamine™2000 transfection reagent. Relative survivin mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. Trypan blue exclusion assays were performed to monitor tumor cell proliferation after siRNA transfection. The cytotoxic effects of etoposide and survivin siRNA, alone and in combination, on leukemic cells were determined using MTT assay. Apoptosis was assessed by ELISA cell death assay. Results: Survivin siRNA markedly reduced both mRNA and protein expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically increased the cell toxic effects of etoposide. Moreover, survivin down-regulation significantly enhanced its induction of apoptosis. Conclusions: Our study suggests that down-regulation of survivin by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an effective adjuvant in AML chemotherapy

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“…20 Survivin is an IAP that appears to be more selectively expressed in malignant The results indicate that survivin may play a key role in tumorigenesis and progression of neuroblsatoma by its biologic activities of anti-apoptosis and angiogenesis. 23 However, it should be acknowledged that this study was retrospective, and therefore has limitations, e.g., in…”

Section: Discussionmentioning

confidence: 95%

COX-2 and Survivin Expression in Neuroblastomas Associated with Tumor Growth and Behavior

Park¹,

Kim

Park

2009

Chonnam Med J

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Angiogenesis and apoptosis are essential in the tumorigenesis and progression of various tumors. Cyclooxygenase-2 (COX-2) and survivin are important factors in these events; however, their roles in neuroblastomas are yet to be delineated. The aim of this study was to evaluate the expression of both COX-2 and survivin in neuroblastomas along with their relationships with tumor angiogenesis, apoptosis, and classical prognostic factors. hirty-nine various-stage neuroblastomas were evaluated for COX-2 expression, microvessel density (MVD), and survivin expression by immunohistochemical methods. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). Thirty-seven cases (94.9%) showed specific expression of COX-2 in the cytoplasm of the tumor cells. COX-2 expression correlated with International Neuroblastoma Staining System (INSS) stage (p=0.004), Shimada histology (p=0.006), and International Neuroblastoma Risk Group (INRG) risk factors (p=0.003). COX-2 expression was positively correlated with MVD (p=0.029), but not with apoptotic index (AI). Thirty-six cases (92.3%) showed positive survivin immunoreactivity, which was observed in the nucleus, cytoplasm, or both of tumor cells. Survivin expression correlated with patient age (p=0.019), INSS stage (p=0.001), and INRG risk factor (p＜0.001). There was a significant difference in AI between the survivin-positive and the survivin-negative groups (p=0.018), and the AI was inversely correlated with survivin. The expression of COX-2 was closely correlated with the expression of survivin. COX-2 and survivin are overexpressed in neuroblastomas, which may play an important role by stimulating tumor angiogenesis and anti-apoptosis in neuroblastomas.

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Survivin, a cancer target with an emerging role in normal adult tissues

Cited by 432 publications

References 136 publications

Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential

Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential

siRNA-mediated Silencing of Survivin Inhibits Proliferation and Enhances Etoposide Chemosensitivity in Acute Myeloid Leukemia Cells

COX-2 and Survivin Expression in Neuroblastomas Associated with Tumor Growth and Behavior

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