Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

Khan, Zakir; Khan, Abdul Arif; Yadav, Hariom; Prasad, G. V. R.; Bisen, Prakash S.

doi:10.1186/s11658-017-0038-0

Cited by 97 publications

(84 citation statements)

References 208 publications

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“…2,10,11 The abnormal expression of survivin in cancers is attributed to various factors, including microRNAs, p53 mutants, nuclear factor-κB, receptor tyrosine kinases, and numerous signaling cascades, such as the PI3K/Akt and signal transducer and activator of transcription-3 (STAT3) pathways. 12,13 Numerous reports have indicated that overexpression of survivin correlates with malignancy, poor clinical outcome, and recurrence of various cancers. 14 Recent studies suggest that survivin is involved in the regulation of cancer stem cells that can increase radiation and drug resistance of cancers.…”

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confidence: 99%

Discovery of inner centromere protein‐derived small peptides for cancer imaging and treatment targeting survivin

et al. 2020

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Survivin belongs to the inhibitor of apoptosis protein family, which is consistently overexpressed in most cancer cells but rarely expressed in normal adult tissues. Therefore, the detection and inhibition of survivin are regarded as attractive strategies for cancer-specific treatment. In this study, we designed and synthesized 7-19 residues of inner centromere protein (INCENP)-derived small peptides (INC peptides) as novel survivin-targeting agents. The INC peptides showed binding affinity for the human survivin protein (K d = 91.4-255 nmol L −1 ); INC 16-22 , which contains residues 16-22 of INCENP, showed the highest affinity (91.4 nmol L −1 ). Confocal fluorescence imaging showed consistent colocalization of FITC-INC 16-22 and survivin in cell lines. Nona-arginine-linked INC 16-22 (r9-INC 16-22 ) rendered INC 16-22 cells penetrable and strongly inhibited cell growth of MIA PaCa-2 cells (52% inhibition at 1.0 µmol L −1 ) and MDA-MB-231 cells (60% inhibition at 10 µmol L −1 ) as determined by MTT assays. The exposure of MIA PaCa-2 cells to 40 µmol L −1 r9-INC 16-22 apparently reduced the intracellular protein expression levels of survivin. However, cleaved caspase-3 was significantly increased in cells treated with r9-INC 16-22 , even at 10 µmol L −1 , compared to untreated cells. Flow cytometry revealed that r9-INC 16-22 strongly induced apoptosis in MIA PaCa-2 cells. These results indicate that the cytotoxic effects of r9-INC 16-22 could be mediated mainly through the disruption of survivin-dependent antiapoptotic functions and partly because of the direct degradation of the survivin protein. Our findings suggest that INC peptides can act as useful scaffolds for novel cancer imaging and anticancer agents. K E Y W O R D S anticancer, apoptosis, cancer imaging, peptide, survivin 1 | INTRODUC TI ON Survivin, the smallest protein (16.5 kDa) among the inhibitor of apoptosis protein (IAP) family, is one of the most cancer-specific proteins 1,2 ; it is highly overexpressed in most cancers, but barely detected in the majority of normal cells. 3-6 Survivin is involved in at least 2 essential cellular processes, inhibition of apoptosis and regulation of the cell cycle. 5 Furthermore, it participates in another antiapoptotic effect by S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Fuchigami T, Ishikawa N, Nozaki I, et al. Discovery of inner centromere protein-derived small peptides for cancer imaging and treatment targeting survivin.

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confidence: 99%

Discovery of inner centromere protein‐derived small peptides for cancer imaging and treatment targeting survivin

et al. 2020

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“…Increases in cleaved caspase 3 and 7 protein levels by treatment with 1 but not with 2 were in good agreement with the activities of caspase 3 and 7. Survivin is a member of the inhibitor of apoptosis protein family, functions as a key regulator of mitosis and apoptosis, and is overexpressed in various cancer cells . This protein indirectly suppresses caspase 3 through regulation of X‐chromosome‐linked inhibitor of apoptosis protein (XIAP) and caspase 9 .…”

Section: Resultsmentioning

confidence: 99%

“…Survivin is a member of the inhibitor of apoptosis protein family, functions as a key regulator of mitosis and apoptosis, and is overexpressed in various cancer cells. [38,39] This protein indirectly suppresses caspase 3 through regulation of X-chromosome-linked inhibitor of apoptosis protein (XIAP) and caspase 9. [38] Snabestari et al [40] showed that CREB silencing in NALM-6 induced downregulation of XIAP and upregulation of cleaved PARP and caspase 3 and 7.…”

Section: Exploration Of Cell Signalling Molecules Involved In Apoptosismentioning

confidence: 99%

“…[38,39] This protein indirectly suppresses caspase 3 through regulation of X-chromosome-linked inhibitor of apoptosis protein (XIAP) and caspase 9. [38] Snabestari et al [40] showed that CREB silencing in NALM-6 induced downregulation of XIAP and upregulation of cleaved PARP and caspase 3 and 7. Other reports have shown that XIAP regulates TAK-1, an upstream signalling molecule of p38 MAPK.…”

Section: Exploration Of Cell Signalling Molecules Involved In Apoptosismentioning

confidence: 99%

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Acrofolione A and B, acetophenone dimers from Acronychia pendunculata, induce an apoptotic effect on human NALM-6 pre-B cell leukaemia cells

Matsui

Ito

Kato

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives We investigated the apoptotic activities of acrofolione A (1) and B (2) isolated from Acronychia pedunculata against a human pre‐B cell leukaemia cell line (NALM‐6) to explore the apoptosis‐related signalling molecules targeted by 1 and 2. Methods The apoptosis effects of 1 and 2 in NALM‐6 cells were investigated by TUNEL staining, annexin V, mitochondria membrane potential and caspase 3/7 activity. We carried out a protein array to explore the signalling molecules involved in apoptosis comprehensively. Key findings Acrofolione A (1) suppressed the growth of NALM‐6, K562 and HPB‐ALL cells (IC50 16.7 ± 1.9, 17.9 ± 0.3 and 10.1 ± 0.2 μm, respectively) more effectively than acrofolione B (2). Both compounds time‐dependently increased the number of NALM‐6 cells with abnormal nuclei, and increased the number of annexin V‐positive cells and decreased the mitochondrial membrane potential of NALM‐6 cells. Acrofolione A (1) markedly elevated caspase 3/7 activity and increased the number of TUNEL‐positive cells. Cells treated with either compound showed enhanced expression of cleaved PARP and cleaved caspase 3 and 7, and reduced survivin protein levels. Conclusions Acrofolione A (1) and B (2) may be useful in the treatment of various types of leukaemia.

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“…The two predominant NSCLC histological phenotypes are adenocarcinoma and squamous cell carcinoma (LUSC) [3]. LUSC is associated with greater mortality and morbidity due to its highly invasive nature that often invades neighboring tissues, and can metastasize distant organs [4].The treatments of the LUSC are often less effective and the chemotherapy remains the major therapeutic choice [5].The mortality is particularly higher in advanced stages compared with early interventions. At the present, LUSC still lacks effective molecular target for developing target therapy.…”

Section: Introductionmentioning

confidence: 99%

Hsa-mir-210 as a novel signature predicts survival in lung squamous cell carcinoma using bioinformatics analysis

Liu

Chen

et al. 2019

Preprint

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In recent years, more and more studies have shown that the expression of miRNAs is closely related to the occurrence of tumors and plays an irreplaceable role in the development and metastasis of tumors. The research was focused on lung squamous cell carcinoma. The data information is downloaded from the TCGA database and analyzed for variance, which is then verified in the GEO database. Then differential expression of miRNAs was found and survival analysis was performed, through the cut -off standard(P<0.05,|logFC|≥2), we screen the 38 up-regulated miRNAs and 14 down-regulated miRNAs from the TCGA. Finally, after the verification on the GEO database, four up-regulated miRNAs (hsa-mir-205, hsa-mir-210, hsa-mir-182, hsa-mir-224) and one downregulated miRNA (hsa-mir-451) were obtained, which provide a new direction for the diagnosis of lung squamous cell carcinoma. In the survival analysis, it was found that the expression state of hsamir-210 was significantly correlated with patient survival. The results in the univariate and multivariate Cox analysis indicated that hsa-mir-210 was an independent prognostic factor on lung squamous cell carcinoma. The functional enrichment analysis showed that hsa-mir-210 was closely related to positive and negative regulation of cell proliferation, DNA transcription, VEGF signaling pathway, MAPK signaling pathway, hif-1 signaling pathway and choline metabolic pathway. In summary, this study suggested that hsa-mir-210 could be a potential prognostic factor for lung squamous cell carcinoma. Key words：LUSC miRNA survival TCGA Author SummaryMicroRNAs are single-stranded small molecular RNA that participate in the regulation of various biological functions through indirect regulation of gene expression, and have been reported to play an important role in the occurrence, development, invasion and metastasis of tumors. In recent years, the research on miRNAs has become increasingly hot, and the role of miRNAs in tumor has been proved more and more. The subjects of this study were squamous cell carcinoma in lung cancer with relatively few studies on miRNAs. Through high-throughput data analysis, miRNAs with differential expression between lung squamous cell carcinoma tissues and normal tissues were found. These differentially expressed miRNAs provide a new direction for the early diagnosis of patients. Then, survival analysis was conducted to find the miRNAs significantly correlated with the total survival time of patients, and multi-factor analysis was conducted to exclude the influence of other clinical factors, and independent risk factors (miRNAs) affecting the survival of patients were determined, so as to provide new targets for the treatment and survival prediction of patients.

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Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

Cited by 97 publications

References 208 publications

Discovery of inner centromere protein‐derived small peptides for cancer imaging and treatment targeting survivin

Discovery of inner centromere protein‐derived small peptides for cancer imaging and treatment targeting survivin

Acrofolione A and B, acetophenone dimers from Acronychia pendunculata, induce an apoptotic effect on human NALM-6 pre-B cell leukaemia cells

Hsa-mir-210 as a novel signature predicts survival in lung squamous cell carcinoma using bioinformatics analysis

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