Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Prabhu, Venugopal Vinod; Siddikuzzaman, Siddikuzzaman; Grace, V. M. Berlin; Guruvayoorappan, Chandrasekharan

doi:10.7314/apjcp.2012.13.8.3539

Cited by 22 publications

(25 citation statements)

References 91 publications

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“…The significance of NDK, including the human NDK species, encoded by the nm23 gene, has been suggested for the pathogenesis of several different forms of severe chronic diseases, including cancers567. In breast and other cancer types, the secretion of NDK from cancer cells has been shown to be critical for increased metastatic activity89. Additionally, the importance of NDK secretion for the establishment of persistent chronic infections by opportunistic pathogens has been well documented151011121314151617.…”

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confidence: 99%

Nucleoside-Diphosphate-Kinase of P. gingivalis is Secreted from Epithelial Cells In the Absence of a Leader Sequence Through a Pannexin-1 Interactome

Atanasova

Lee

Roberts

et al. 2016

Sci Rep

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Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P. gingivalis-NDK impacts this pathway. Ultrastructural and confocal microscopy of P. gingivalis-co-cultured GECs or green-fluorescent-protein (GFP)-P. gingivalis-NDK transfected GECs revealed a perinuclear/cytoplasmic localization of NDK. eATP stimulation induced NDK recruitment to the cell periphery. Depletion of PNX1 by siRNA or inhibition by probenecid resulted in significant blocking of extracellular NDK activity and secretion using ATPase and ELISA assays. Co-immunoprecipitation-coupled Mass-spectrometry method revealed association of P. gingivalis-NDK to the myosin-9 motor molecule. Interestingly, inhibition of myosin-9, actin, and lipid-rafts, shown to be involved in PNX1-hemichannel function, resulted in marked intracellular accumulation of NDK and decreased NDK secretion from infected GECs. These results elucidate for the first time PNX1-hemichannels as potentially main extracellular translocation pathway for NDKs from an intracellular pathogen, suggesting that PNX1-hemichannels may represent a therapeutic target for chronic opportunistic infections.

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confidence: 99%

Nucleoside-Diphosphate-Kinase of P. gingivalis is Secreted from Epithelial Cells In the Absence of a Leader Sequence Through a Pannexin-1 Interactome

Atanasova

Lee

Roberts

et al. 2016

Sci Rep

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“…Among metastasis-suppressor genes, KiSS-1 is the only one that binds to a G-protein coupled receptor (GPR54 or AXOR12 or hOT7T175) and is believed to act late in the metastatic cascade by preventing growth of the metastatic deposit, as opposed to early metastasis suppressor genes [Non metastasis genes (Nm23, KAI1)] that suppress cell detachment and migration from the primary tumor (Bari et al, 2009;Prabhu et al, 2012). KiSS-1 (formerly known as metastin) occur naturally in human placenta which was named for its role as a suppressor sequence (SS); the letters "Ki" were appended to the prefix "SS" to form "KiSS" in homage to the location of its discovery, Hershey, Pennsylvania, home of the famous "Hershey Chocolate KiSSes" (Kotani et al, 2001;Shevde et al, 2003;Iiizumi et al, 2008;Smith and Theodorescu, 2009).…”

Section: Introductionmentioning

confidence: 99%

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

Prabhu

Sakthivel²,

Guruvayoorappan³

2013

Asian Pacific Journal of Cancer Prevention

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“…Ayrıca yüksek RNA seviyeleri ve immünolojik cevap korele bulunmadığı için melanoma hücrelerindeki intrinsik agresivite ile ilişkili olabileceği düşünülmüştür 9 . Ayrca düşük nm23 ekspresyonunun metastaz oranını arttırdığını ve nm23'e ait gen ekspresyonunun regülasyonunun tümör tedavisinde kullanılabileceğini gösteren çalışmalar yapılmıştır 10,11 . Hart ve Easty makalelerinde nm23 geninin tümör hücrelerinde sellüler diferansiasyon ve morfolojik patern oluşumuna katkısının olup olmadığı konusunda şüpheler bulunduğunu bildirmişlerdir 12 .…”

Section: Discussionunclassified

Comparison of prognostic histopathological features in malignant melanoma with the expression of nm23 and p16 proteins

Özsoy¹,

Seçkin²

2015

TURKDERM

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Background and Design:The aim of the study was to evaluate the correlation between prognostic histopathological factors in malignant melanoma (MM) and the expression of nm23 and p16 proteins and to investigate the value of these proteins as a prognostic factor. Materials and Methods: Breslow index, Clark level, presence of ulceration and lymphocytic infiltration were evaluated in HE sections of 40 malignant melanoma cases. UV light exposure of tumor locations was also recorded. Nm23 and p16 antibodies were applied on the tumor sections and immunoreactivity was evaluated semi-quantitatively. Results: According to the extent of expression, nm23 protein was correlated with lymphocytic infiltration (p=0.00), where it was inversely proportional with Breslow index (p=0.022). No statistically significant correlation was determined between expression of this protein and Clark level (p=0.082) and ulceration (p=0.25). According to the intensity, expression of nm23 protein was correlated with lymphocytic infiltration (p=0.00) and it was inversely proportional with Breslow index (p=0.002), Clark level (p=0.004) and ulceration (p=0.014). The expression of p16 protein was correlated with lymphocytic infiltration according to both extensiveness and intensity (p=0.003, p=0.012, respectively), but it was correlated with ulceration according to intensity only (p=0.014). No statistically significant correlation of expression of p16 protein with Breslow index (p=0.129, p=0.174) and Clark level (p=0.072, p=0.08) was determined. UV light exposure and expression of both nm23 (p=0.877, p=0.563) and p16 (p=0.47, p=0.810) proteins were not statistically correlated.

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Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Cited by 22 publications

References 91 publications

Nucleoside-Diphosphate-Kinase of P. gingivalis is Secreted from Epithelial Cells In the Absence of a Leader Sequence Through a Pannexin-1 Interactome

Nucleoside-Diphosphate-Kinase of P. gingivalis is Secreted from Epithelial Cells In the Absence of a Leader Sequence Through a Pannexin-1 Interactome

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

Comparison of prognostic histopathological features in malignant melanoma with the expression of nm23 and p16 proteins

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