Programmed cell death 6 (PDCD6) as a prognostic marker for gastric cancers

Yoon, Jung Hwan; Choi, Yoo Jin; Kim, Sung Geun; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

doi:10.1007/s13277-011-0280-4

Cited by 22 publications

(20 citation statements)

References 20 publications

(30 reference statements)

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“…These resistance isolates had their own antifungal resistance profiles, indicating that these mutations may have originally existed in the A. fumigatus strain and also suggesting that evolved lineages (isolates) may acquire azole resistance independently, while algA defects made the drug-resistant alleles much easier to isolate. Since the algA homolog in humans has a role in apoptotic cell death, this suggests that the loss of algA in fungal cells may allow them to more easily escape from cell apoptosis induced by itraconazole and result in survival mutants conferring drug resistance (33). In addition, of 11 selected independent itraconazole-resistant representatives, we found that they all had various MEC values of caspofungin, suggesting that the cell wall synthesis-related drug target of caspofungin in some isolates may be changed.…”

Section: Discussionmentioning

confidence: 99%

Screening and Characterization of a Non- cyp51A Mutation in an Aspergillus fumigatus cox10 Strain Conferring Azole Resistance

Wei

Chen

Gao

et al. 2017

Antimicrob Agents Chemother

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The rapid and global emergence of azole resistance in the human pathogen Aspergillus fumigatus has drawn attention. Thus, a thorough understanding of its mechanisms of drug resistance requires extensive exploration. In this study, we found that the loss of the putative calcium-dependent protein-encoding gene algA causes an increased frequency of azole-resistant A. fumigatus isolates. In contrast to previously identified azole-resistant isolates related to cyp51A mutations, only one isolate carries a point mutation in cyp51A (F219L mutation) among 105 independent stable azole-resistant isolates. Through next-generation sequencing (NGS), we successfully identified a new mutation (R243Q substitution) conferring azole resistance in the putative A. fumigatus farnesyltransferase Cox10 (AfCox10) (AFUB_065450). High-performance liquid chromatography (HPLC) analysis verified that the decreased absorption of itraconazole in related Afcox10 mutants is the primary reason for itraconazole resistance. Moreover, a complementation experiment by reengineering the mutation in a parental wild-type background strain demonstrated that both the F219L and R243Q mutations contribute to itraconazole resistance in an algAindependent manner. These data collectively suggest that the loss of algA results in an increased frequency of azole-resistant isolates with a non-cyp51A mutation. Our findings indicate that there are many unexplored non-cyp51A mutations conferring azole resistance in A. fumigatus and that algA defects make it possible to isolate drug-resistant alleles. In addition, our study suggests that genome-wide sequencing combined with alignment comparison analysis is an efficient approach to identify the contribution of single nucleotide polymorphism (SNP) diversity to drug resistance.KEYWORDS Aspergillus fumigatus, azole resistance, cox10, cyp51A, mutation T he filamentous fungus Aspergillus fumigatus, one of the major opportunistic fungal pathogens, causes invasive fungal infections (IFIs) among immunosuppressed patients, with a high mortality rate (1, 2). Currently, azole compounds are the primary clinical therapy drug for IFIs and have been widely used in agriculture as well (3, 4). However, with the emergence of azole-resistant isolates, the efficacy of azole antifungals has been restricted so that azole resistance is becoming a growing public health menace (5-8). Therefore, the identification of genes whose mutations lead to drug resistance can provide a complete understanding of the molecular mechanisms underlying azole resistance.Previous studies verified that the most common mechanisms of resistance to azole antifungals observed in A. fumigatus samples are due to Cyp51A mutations, which

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Section: Discussionmentioning

confidence: 99%

Screening and Characterization of a Non- cyp51A Mutation in an Aspergillus fumigatus cox10 Strain Conferring Azole Resistance

Wei

Chen

Gao

et al. 2017

Antimicrob Agents Chemother

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“…Apoptosis serves an important role in the progression of ovarian cancer (13), and certain papers have suggested that human chorionic gonadotropin or LH may inhibit cisplatin-induced apoptosis in ovarian cancer cells (14,15). PDCD6 is an important apoptotic mediator and a prognostic marker for gastric cancer (16); it is also an independent predictor of progression-free survival in patients with epithelial ovarian cancer (7). Park et al (17) demonstrated that PDCD6 additively cooperated with anticancer drugs through the activation of nuclear factor-κB pathways.…”

Section: Discussionmentioning

confidence: 99%

Luteinizing hormone inhibits cisplatin-induced apoptosis in human epithelial ovarian cancer cells

et al. 2016

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Abstract. The elevation of Luteinizing hormone (LH) is commonly observed in epithelial ovarian cancer. This correlation suggests a causal relationship between LH and ovarian cancer. LH has been reported to inhibit apoptosis in ovarian cancer cells. Programmed cell death gene 6 (PDCD6), also known as apoptosis-linked gene-2, is an apoptotic mediator that is required for apoptosis to numerous death stimuli. Therefore, the aim of the present study was to determine whether PDCD6 may be induced by LH in ovarian cancer, and whether LH may affect the apoptosis through PDCD6. Flow cytometry was used to detect the effects of cisplatin on the induction of apoptosis by LH. PDCD6 expression was monitored by quantitative polymerase chain reaction and western blotting. The signaling transduction pathways were also investigated by western blotting. The present study demonstrated that LH reduced cisplatin-induced apoptosis in ovarian OVCAR-3 and SKOV-3 cancer cells. The results indicated that PDCD6 expression was inhibited by LH. In addition, the inhibition of PDCD6, induced by LH, was mediated through the activation of the phosphatidylinositol 3-kinase/protein kinase B and p44/42 mitogen-activated protein kinase transduction signaling pathways. The present results suggest that LH affects the sensitivity of ovarian cancer cells to chemotherapy, primarily by signaling to inhibit apoptosis and to additionally suppress PDCD6.

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“…Among them, some important factors should be noticed. For example, one of down-regulated protein, programmed cell death protein 6 (PDCD6), also called apoptosislinked gene 2 protein (ALG2), functions as calciumbinding protein required for T cell receptor-, Fas-, and glucocorticoid-induced cell death (Suzuki et al 2012;Yoon et al 2012). Besides their multifunction, four proteins, ATP-dependent RNA helicase DDX39A, complement component 1 Q subcomponent-binding protein (SF2p32), Lamin-A/C, and far upstream element-binding Protein 2 are involved in pre-mRNA splicing or as splicing factors to play an important role in DNA damage and repair (Dittmer and Misteli 2011;Filippov et al 2007;Marengo and Wassarman 2008;Singh et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomics analysis of global cellular stress responses to hydroxyurea-induced DNA damage in HeLa cells

et al. 2014

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Both environmental agents and spontaneous cellular events cause serious DNA damage, threatening the integrity of the genome. In response to replication stress or genotoxic agents triggered DNA damage, degradation of p12 subunit of DNA polymerase delta (Pol d) results in an inter-conversion between heterotetramer (Pol d4) and heterotrimer (Pol d3) forms and plays a significant role in DNA damage response in eukaryotic cells. In this work, we used mass spectrometry-based proteomic approach to identify those cellular stress response protein changes corresponding to the degradation of p12 in DNAdamaged HeLa cells by the treatment with hydroxyurea (HU). A total of 736 ± 13 proteins in non-treated control group and 741 ± 19 protein spots in HUtreated cells were detected, of which 34 proteins (17 up-regulated and 17 down-regulated) exhibited significantly altered protein expression levels. Their physiological roles are mainly associated with cellular components, molecular functions, and biological processes by gene ontology analysis, among which 21 proteins were mapped to KEGG pathways. They are involved in 5 primary pathways with the subsets involving 16 secondary pathways by further KEGG analysis. More interestingly, the up-regulation of translationally controlled tumor protein was further identified to be associated with p12 degradation by Western blot analysis. Our works may enlarge and broaden our view for deeply understanding how global cellular stress responds to DNA damage, which could contribute to the etiology of human cancer or other diseases that can result from loss of genomic stability.

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Programmed cell death 6 (PDCD6) as a prognostic marker for gastric cancers

Cited by 22 publications

References 20 publications

Screening and Characterization of a Non- cyp51A Mutation in an Aspergillus fumigatus cox10 Strain Conferring Azole Resistance

Screening and Characterization of a Non- cyp51A Mutation in an Aspergillus fumigatus cox10 Strain Conferring Azole Resistance

Luteinizing hormone inhibits cisplatin-induced apoptosis in human epithelial ovarian cancer cells

Comparative proteomics analysis of global cellular stress responses to hydroxyurea-induced DNA damage in HeLa cells

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