The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence

Wall, Meaghan, Poortinga, Gretchen, Stanley, Kym L., Lindemann, Ralph K., Bots, Michael, Chan, Christopher J., Bywater, Megan J., Kinross, Kathryn M., Astle, Megan V., Waldeck, Kelly, Hannan, Katherine M., Shortt, Jake, Smyth, Mark J., Lowe, Scott W., Hannan, Ross D., Pearson, Richard B., Johnstone, Ricky W. and McArthur, Grant A. (2013) The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence. Cancer Discovery, 3 1: 82-95. doi:10.1158/2159-8290.CD-12-0404

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ292618_OA.pdf Full text (open access) application/pdf 4.70MB 0

Author Wall, Meaghan
Poortinga, Gretchen
Stanley, Kym L.
Lindemann, Ralph K.
Bots, Michael
Chan, Christopher J.
Bywater, Megan J.
Kinross, Kathryn M.
Astle, Megan V.
Waldeck, Kelly
Hannan, Katherine M.
Shortt, Jake
Smyth, Mark J.
Lowe, Scott W.
Hannan, Ross D.
Pearson, Richard B.
Johnstone, Ricky W.
McArthur, Grant A.
Title The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence
Formatted title
The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence
Journal name Cancer Discovery   Check publisher's open access policy
ISSN 2159-8274
2159-8290
Publication date 2013-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1158/2159-8290.CD-12-0404
Open Access Status DOI
Volume 3
Issue 1
Start page 82
End page 95
Total pages 14
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Abstract MYC deregulation is common in human cancer. IG-MYC translocations that are modeled in EμMyc mice occur in almost all cases of Burkitt lymphoma as well as in other B-cell lymphoproliferative disorders. Deregulated expression of MYC results in increased mTOR complex 1 (mTORC1) signaling. As tumors with mTORC1 activation are sensitive to mTORC1 inhibition, we used everolimus, a potent and specific mTORC1 inhibitor, to test the requirement for mTORC1 in the initiation and maintenance of EμMyc lymphoma. Everolimus selectively cleared premalignant B cells from the bone marrow and spleen, restored a normal pattern of B-cell differentiation, and strongly protected against lymphoma development. Established EμMyc lymphoma also regressed after everolimus therapy. Therapeutic response correlated with a cellular senescence phenotype and induction of p53 activity. Therefore, mTORC1-dependent evasion of senescence is critical for cellular transformation and tumor maintenance by MYC in B lymphocytes.
Keyword MYC deregulation
IG-MYC
Burkitt lymphoma
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online first: 14 December 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 35 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 35 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 03 Mar 2013, 10:52:15 EST by System User on behalf of School of Biomedical Sciences