Inhibition of telomerase activity by NME2: impact on metastasis suppression?

Kar, Anirban; Chowdhury, Shantanu

doi:10.1007/s00210-014-1077-y

Cited by 8 publications

(5 citation statements)

References 49 publications

(61 reference statements)

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“…This was independent of the nuclease activity of NM23-H2, suggesting that NM23-H2 did not suppress telomerase activity by cleaving the template DNA necessary for telomere elongation by hTERT [ 5 ]. As expected, the prolonged over-expression of NM23-H2 resulted in telomere shortening in MDA-MB-231 breast cancer cells, further supporting the role of NM23-H3 in the suppression of telomerase activity [ 27 ].…”

Section: Direct Interaction Of Nm23 Proteins With Telomeres and Tesupporting

confidence: 68%

Emerging Molecular Connections between NM23 Proteins, Telomeres and Telomere-Associated Factors: Implications in Cancer Metastasis and Ageing

Sharma

Sengupta

Chowdhury

2021

IJMS

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The metastasis suppressor function of NM23 proteins is widely understood. Multiple enzymatic activities of NM23 proteins have also been identified. However, relatively less known interesting aspects are being revealed from recent developments that corroborate the telomeric interactions of NM23 proteins. Telomeres are known to regulate essential physiological events such as metastasis, ageing, and cellular differentiation via inter-connected signalling pathways. Here, we review the literature on the association of NM23 proteins with telomeres or telomere-related factors, and discuss the potential implications of emerging telomeric functions of NM23 proteins. Further understanding of these aspects might be instrumental in better understanding the metastasis suppressor functions of NM23 proteins.

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Section: Direct Interaction Of Nm23 Proteins With Telomeres and Tesupporting

confidence: 68%

Emerging Molecular Connections between NM23 Proteins, Telomeres and Telomere-Associated Factors: Implications in Cancer Metastasis and Ageing

Sharma

Sengupta

Chowdhury

2021

IJMS

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“…To gain some understanding of the underlying mechanisms responsible for the different expression programs, we identified the top expressed transcription factors in each cluster (Figure 6d). NME2, implicated as a transcriptional regulator acting directly as a DNA‐binding transcription factor and displaying indirect effects on gene expression programs by affecting telomerase activity and telomere length (Kar & Chowdhury, 2015; Puts et al, 2018), had relatively higher expression in Cluster 5. KLF2, which plays a role in regulating NK cell proliferation, survival, and migration (Rabacal et al, 2016, p. 2), showed broad expression among cells in Cluster 2 compared to cells expanded with mIL15.…”

Section: Resultsmentioning

confidence: 99%

Differential effects on natural killer cell production by membrane‐bound cytokine stimulations

Chang

Tang

Nelson

et al. 2022

Biotech & Bioengineering

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Robust manufacturing production of natural killer (NK) cells has been challenging in allogeneic NK cell-based therapy. Here, we compared the impact of cytokines on NK cell expansion by developing recombinant K562 feeder cell lines expressing membrane-bound cytokines, mIL15, mIL21, and 41BBL, individually or in combination. We found that 41BBL played a dominant role in promoting up to 500,000-fold of NK cell expansion after a 21-day culture process without inducing exhaustion.However, 41BBL stimulation reduced the overall cytotoxic activity of NK cells when combined with mIL15 and/or mIL21. Additionally, long-term stimulation with mIL15 and/or mIL21, but not 41BBL, increased CD56 expression and the CD56 bright population, which is unexpectedly correlated with NK cell cytotoxicity. By conducting single-cell sequencing, we identified distinct subpopulations of NK cells induced by different cytokines, including an adaptive-like CD56 bright CD16 -CD49a + subset induced by mIL15. Through gene expression analysis, we found that different cytokines modulated signaling pathways and target genes involved in cell cycle, senescence, self-renewal, migration, and maturation in different ways. Together, our study demonstrates that cytokine signaling pathways play distinct roles in NK cell

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“…The role of the highly homologous isoform NME2 in metastasis dissemination remains much less documented and controversial. [83][84][85][86][87] Our most recent data demonstrate a major role of NME1, not of NME2, during the transition of breast carcinoma from in situ to invasive (Mathieu Boissan, unpublished data).…”

Section: Nme In Metastasismentioning

confidence: 85%

The NDPK/NME superfamily: state of the art

Boissan

Schlattner

Lacombe

2018

Laboratory Investigation

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Nucleoside diphosphate kinases (NDPK) are nucleotide metabolism enzymes encoded by NME genes (also called NM23). Given the fact that not all NME-encoded proteins are catalytically active NDPKs and that NM23 generally refers to clinical studies on metastasis, we use here NME/NDPK to denote the proteins. Since their discovery in the 1950's, NMEs/NDPKs have been shown to be involved in multiple physiological and pathological cellular processes, but the molecular mechanisms have not been fully determined. Recent progress in elucidating these underlying mechanisms has been presented by experts in the field at the 10th International Congress on the NDPK/NME/AWD protein family in October 2016 in Dubrovnik, Croatia, and is summarized in review articles or original research in this and an upcoming issue of Laboratory Investigation. Within this editorial, we discuss three major cellular processes that involve members of the multi-functional NME/NDPK family: (i) cancer and metastasis dissemination, (ii) membrane remodeling and nucleotide channeling, and iii) protein histidine phosphorylation.

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Inhibition of telomerase activity by NME2: impact on metastasis suppression?

Cited by 8 publications

References 49 publications

Emerging Molecular Connections between NM23 Proteins, Telomeres and Telomere-Associated Factors: Implications in Cancer Metastasis and Ageing

Emerging Molecular Connections between NM23 Proteins, Telomeres and Telomere-Associated Factors: Implications in Cancer Metastasis and Ageing

Differential effects on natural killer cell production by membrane‐bound cytokine stimulations

The NDPK/NME superfamily: state of the art

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