Imperial College London
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DrSilviaOttaviani

Faculty of Medicine, Department of Surgery & Cancer

Honorary Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2823silvia.ottaviani

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zagorac:2021:10.1158/0008-5472.CAN-20-2612,
author = {Zagorac, S and de, Giorgio A and Dabrowska, A and Kalisz, M and Casas-Vila, N and Cathcart, P and Yiu, A and Ottaviani, S and Degani, N and Lombardo, Y and Tweedie, A and Nissan, T and Vance, KW and Ulitsky, I and Stebbing, J and Castellano, L},
doi = {10.1158/0008-5472.CAN-20-2612},
journal = {Cancer Research},
pages = {580--593},
title = {SCIRT lncRNA restrains tumorigenesis by opposing transcriptional programs of tumor-initiating cells.},
url = {http://dx.doi.org/10.1158/0008-5472.CAN-20-2612},
volume = {81},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - In many tumors, cells transition reversibly between slow-proliferating tumor-initiating cells (TIC) and their differentiated, faster-growing progeny. Yet how transcriptional regulation of cell cycle and self-renewal genes is orchestrated during these conversions remains unclear. In this study, we show that as breast TIC form, a decrease in cell-cycle and increase in self-renewal gene expression is coregulated by SOX2 and EZH2, which colocalize at CpG islands. This pattern was negatively controlled by a novel long non-coding RNA (lncRNA) that we name SCIRT, which was markedly upregulated in tumorspheres but colocalized with and counteracted EZH2 and SOX2 during cell cycle and self-renewal regulation to restrain tumorigenesis. SCIRT specifically interacted with EZH2 to increase EZH2 affinity to FOXM1 without binding the latter. In this manner, SCIRT induced transcription at cell cycle gene promoters by recruiting FOXM1 through EZH2 to antagonize EZH2-mediated effects at target genes. Conversely, on stemness genes, FOXM1 was absent and SCIRT antagonized EZH2 and SOX2 activity, balancing towards repression. These data suggest that the interaction of a lncRNA with EZH2 can alter the affinity of EZH2 for its protein binding partners to regulate cancer cell state transitions.
AU  - Zagorac,S
AU  - de,Giorgio A
AU  - Dabrowska,A
AU  - Kalisz,M
AU  - Casas-Vila,N
AU  - Cathcart,P
AU  - Yiu,A
AU  - Ottaviani,S
AU  - Degani,N
AU  - Lombardo,Y
AU  - Tweedie,A
AU  - Nissan,T
AU  - Vance,KW
AU  - Ulitsky,I
AU  - Stebbing,J
AU  - Castellano,L
DO  - 10.1158/0008-5472.CAN-20-2612
EP  - 593
PY  - 2021///
SN  - 0008-5472
SP  - 580
TI  - SCIRT lncRNA restrains tumorigenesis by opposing transcriptional programs of tumor-initiating cells.
T2  - Cancer Research
UR  - http://dx.doi.org/10.1158/0008-5472.CAN-20-2612
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33172932
UR  - https://cancerres.aacrjournals.org/content/early/2020/11/10/0008-5472.CAN-20-2612
UR  - http://hdl.handle.net/10044/1/84149
VL  - 81
ER  -
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