Notch1 ligand signaling pathway activated in cervical cancer: poor prognosis with high-level JAG1/Notch1

Yousif, Nasser Ghaly; Sadiq, Alaa M.; Yousif, Maitham G.; Al-Mudhafar, Rihab H.; Albaghdadi, J.; Hadi, Najah R.

doi:10.1007/s00404-015-3694-1

Cited by 35 publications

(30 citation statements)

References 27 publications

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“…Notch pathway is reported to be an evolutionarily conserved signaling system which is able to regulate cell differentiation, proliferation, cell‐fate determination as well as the self‐renewal of progenitor cells and stem cells in both adult and embryonic organs . Notch signaling pathway participates in the process of neo‐plastic transformation in different cell types, such as cervical cancer and lung cancer . It was reported that elevated expression of Notch signaling pathway was able to contribute to the apoptosis of cervical cancer cells, while decreased expression of Notch l could inhibit the development and prognosis of cervical cancer .…”

Section: Introductionmentioning

confidence: 99%

Retracted: Inhibition of Notch signaling pathway enhanced the radiosensitivity of breast cancer cells

Peng

Xiao-lin

Ran

et al. 2018

J of Cellular Biochemistry

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This study aimed to investigate the effect of inhibiting the Notch signaling pathway on the radiosensitivity of breast cancer cells. Human breast cancer cell lines (MCF-7 and T47D) were selected and treated with radiation of different doses. Cells were treated with Gamma secretase inhibitor (GSI) to analyze the effects of GSI on the Notch signaling, which were detected by Immunofluorescence assay, RT-qPCR, and Western blot analysis. Besides, Transwell assay, Scratch test, colony formation assay, MTT assay, and flow cytometry were conducted to show the effects of GSI on the invasion and migration, survival fraction, cell viability, and apoptosis of MCF-7 and T47D cells after radiation therapy. Moreover, cell transfection with a dominant negative mutant of RBPJ, the key transcription factor of Notch signaling pathway, were also applied to show the inhibition of Notch signaling pathway. Initially, we found that the 4 Gy radiation activated Notch signaling pathway, and enhanced the invasion and migration of MCF-7 and T47D cells. However, GSI inhibited the Notch signaling pathway, and reversed the enhancement of radiation on the migration and invasion, promoted the enhancement of apoptosis and inhibition of proliferation of MCF-7 and T47D cells induced by radiation. Except that, we also determined that GSI and dnRBPJ suppressed the upregulation of Notch signaling after radiation therapy. Our study demonstrated that inhibition of the Notch signaling pathway enhanced the radiosensitivity of breast cancer cells, which may provide evident for a beneficial adjuvant therapy in the breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Retracted: Inhibition of Notch signaling pathway enhanced the radiosensitivity of breast cancer cells

Peng

Xiao-lin

Ran

et al. 2018

J of Cellular Biochemistry

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“…24, 25 For instance, Jag1 expression has been found to be upregulated and its levels inversely associated with patient's survival in breast, colon and cervical cancers. 26, 27, 28 Also, silencing of Jag1 in human prostate cancer cells decreases cell invasion and in vivo tumour growth. 29 However, the functional contribution of Jag1 in ICC development has not been studied to date.…”

Section: Introductionmentioning

confidence: 99%

Jagged 1 is a major Notch ligand along cholangiocarcinoma development in mice and humans

et al. 2016

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Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts. Furthermore, we found that while overexpression of Jag1 alone does not lead to liver tumour development, overexpression of Jag1 synergizes with activated AKT signalling to promote liver carcinogenesis in AKT/Jag1 mice. Histologically, tumours consisted exclusively of ICC, with hepatocellular tumours not occurring in AKT/Jag1 mice. Furthermore, tumours from AKT/Jag1 mice exhibited extensive desmoplastic reaction, an important feature of human ICC. At the molecular level, we found that both AKT/mTOR and Notch cascades are activated in AKT/Jag1 ICC tissues, and that the Notch signalling is necessary for ICC development in AKT/Jag1 mice. In human ICC cell lines, silencing of Jag1 via specific small interfering RNA reduces proliferation and increases apoptosis. Finally, combined inhibition of AKT and Notch pathways is highly detrimental for the in vitro growth of ICC cell lines. In summary, our study demonstrates that Jag1 is an important upstream inducer of the Notch signalling in human and mouse ICC. Targeting Jag1 might represent a novel therapeutic strategy for the treatment of this deadly disease.

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“…Sergant gimdos kaklelio vėžiu yra suaktyvėjusi JAG2 mRNR ir padidėjusi JAG1 raiška (19). Viename iš tyrimų nustatyta, kad esant didesnei NOTCH1 ir JAG1 baltymų raiškai bendrasis pacienčių išgyvenamu-mas yra blogesnis, palyginti su išgyvenamumu tų pacienčių, kurių navike minėtų komponentų raiš-ka mažesnė (20). Kituose tyrimuose konstatuota padidėjusi NOTCH3 baltymo raiška invazinės gimdos kaklelio karcinomos atveju, palyginti su NOTCH3 raiška esant ikivėžiniams gimdos kaklelio pakitimams bei jo raiška normaliame gimdos kaklelio audinyje.…”

Section: Notch Signalinio Kelio Vaidmuo Formuojantis Ginekologiniams unclassified

NOTCH signalinio kelio ir ginekologinių piktybinių navikų sąsaja

Lachej¹,

Dabkevičienė²,

Sasnauskienė³

et al. 2017

AML

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Vilniaus universitetas, Gamtos mokslų fakultetas, Biochemijos ir molekulinės biologijos katedra 3 Nacionalinis vėžio institutas, Konsultacinė poliklinika 4 Nacionalinis vėžio institutas, Mokslinių tyrimų centrasĮvadas. Organizmo ląstelėse vykstančius procesus kontroliuoja įvairūs signaliniai keliai. Vienas iš jų yra NOTCH signalinis kelias. Nustatyta, kad dalinis NOTCH funkcijos praradimas arba nenormalus NOTCH signalo aktyvinimas susijęs su įvairiais žmogaus vystymosi sutrikimais ir ligomis.Medžiaga ir metodika. Pagrindinis informacijos šaltinis ieš-kant duomenų -PubMed duomenų bazė.Rezultatai. Straipsnyje nagrinėjama onkologinių ligų bei NOTCH signalinio kelio dalyvių sąsaja. NOTCH signalas, vystantis vėžiui, gali veikti dvejopai: kaip onkogenas ir kaip naviko augimo slopiklis. Tikslus tokio poveikio mechanizmas dar nėra žinomas. NOTCH signalinio kelio tyrimai svarbūs siekiant atrasti naujus vėžio gydymo būdus, farmakologiniais ir genetiniais metodais valdant NOTCH signalinį kelią. Šioje apžvalgoje daugiausia dėmesio skiriama ginekologiniams piktybiniams navikams, ypač gimdos kūno vėžiui.Išvados. Pastarųjų metų mokslinių tyrimų duomenys rodo, kad NOTCH signalinis kelias yra neabejotinai svarbus formuojantis gimdos kūno vėžiui, todėl jo komponentai gali būti potencialūs prognoziniai biožymenys ir molekuliniai terapiniai taikiniai. Siekiant patikslinti NOTCH signalinio kelio dalyvių reikšmę bei jų sąveiką su kitų signalinių kelių dalyviais, kurie taip pat gali būti svarbūs formuojantis ir progresuojant gimdos kūno vėžiui, reikalingi tolesni šios srities moksliniai tyrimai. Raktažodžiai: NOTCH signalinis kelias, onkoginekologinės ligos ĮVADASProcesus, kai iš vienos ląstelės susidaro daugialąstis organizmas, reguliuoja darni genų veikla, kurią kontroliuoja įvairūs signaliniai keliai. Vienas svarbus, nulemiantis ląstelės likimą, yra NOTCH signalinis kelias; signalo perdavimas šiuo keliu būdingas evoliuciškai skirtingiems organizmams -nuo jūrų ežio iki žmogaus. Signalas, perduodamas per NOTCH signalinio kelio receptorius ir veikdamas kartu su įvairiais ląstelės komponentais, daro įtaką ląstelės diferenciacijos, proliferacijos ir apoptozės procesams (1-3).Pirmą kartą geną, koduojantį NOTCH signalinio kelio receptorių, paminėjo T. H. Morganas beveik prieš 100 metų darbe "Geno teorija". Jis kryžmini-mo būdu išvedė mutantines "NOTCH" museles su

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Notch1 ligand signaling pathway activated in cervical cancer: poor prognosis with high-level JAG1/Notch1

Abstract: The present data proved the over-expression of Notch1/JAGD1 and its association with tumor progression in human cervical cancer, which might be a potential valuable biomarker for cervical cancer and further studies need.

Cited by 35 publications

References 27 publications

Retracted: Inhibition of Notch signaling pathway enhanced the radiosensitivity of breast cancer cells

Retracted: Inhibition of Notch signaling pathway enhanced the radiosensitivity of breast cancer cells

Jagged 1 is a major Notch ligand along cholangiocarcinoma development in mice and humans

NOTCH signalinio kelio ir ginekologinių piktybinių navikų sąsaja

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