@article{5e75088fe1c64381bf0fb0fb076a0c71,
title = "Suppression of p16 Induces mTORC1-Mediated Nucleotide Metabolic Reprogramming",
abstract = "Senescence bypass through p16 loss predisposes to transformation and tumorigenesis. Buj et al. found that the loss of p16 upregulates nucleotide metabolism through increased mTORC1-mediated translation of RPIA to bypass senescence in an RB-independent manner. Thus, the mTORC1-RPIA axis is a metabolic vulnerability for p16-null cancers.",
keywords = "BRAF, cancer metabolism, cell cycle, melanoma, nevi, pancreatic cancer, pentose phosphate pathway, ribonucleotide reductase M2, ribose-5-phosphate isomerase A, senescence",
author = "Raquel Buj and Chen, {Chi Wei} and Dahl, {Erika S.} and Leon, {Kelly E.} and Rostislav Kuskovsky and Natella Maglakelidze and Maithili Navaratnarajah and Gao Zhang and Doan, {Mary T.} and Helen Jiang and Michael Zaleski and Lydia Kutzler and Holly Lacko and Yiling Lu and Mills, {Gordon B.} and Raghavendra Gowda and Robertson, {Gavin P.} and Warrick, {Joshua I.} and Meenhard Herlyn and Yuka Imamura and Kimball, {Scot R.} and DeGraff, {David J.} and Snyder, {Nathaniel W.} and Aird, {Katherine M.}",
note = "Funding Information: We would like to acknowledge Dr. Alice Soragni (UCLA), Dr. Kristin Eckert and Dr. Nadine Hempel (Penn State College of Medicine), Dr. Gina DeNicola (Moffitt Cancer Center), and Dr. Rugang Zhang (The Wistar Institute) for providing cell lines. We would like to thank Drs. Juan Andres Melendez and Robert P. Feehan for providing helpful discussion. This work was supported by grants from the NIH ( F31CA236372 to E.S.D., P50CA174523 and U54CA224070 to M.H., R01DK13499 and R01K156548 to S.R.K., K22ES026235 and R01GM132261 to N.W.S., and R00CA194309 to K.M.A.); the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.H.); the W.W. Smith Charitable Trust (to K.M.A.); and the Penn State Cancer Institute Postdoctoral Fellowship (to R.B.). The RPPA Core Facility is funded by NCI P30CA16672 . Funding Information: We would like to acknowledge Dr. Alice Soragni (UCLA), Dr. Kristin Eckert and Dr. Nadine Hempel (Penn State College of Medicine), Dr. Gina DeNicola (Moffitt Cancer Center), and Dr. Rugang Zhang (The Wistar Institute) for providing cell lines. We would like to thank Drs. Juan Andres Melendez and Robert P. Feehan for providing helpful discussion. This work was supported by grants from the NIH (F31CA236372 to E.S.D. P50CA174523 and U54CA224070 to M.H. R01DK13499 and R01K156548 to S.R.K. K22ES026235 and R01GM132261 to N.W.S. and R00CA194309 to K.M.A.); the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.H.); the W.W. Smith Charitable Trust (to K.M.A.); and the Penn State Cancer Institute Postdoctoral Fellowship (to R.B.). The RPPA Core Facility is funded by NCI P30CA16672. Conceptualization, R.B. and K.M.A.; Methodology, R.K. Y.I. and N.W.S.; Investigation, R.B. C.-W.C. E.S.D. K.E.L. R.K. N.M. M.N. M.T.D. H.J. M.Z. L.K. H.L. Y.I. N.W.S. and K.M.A.; Resources, G.Z. R.G. G.R. J.I.W. M.H. and D.J.D.; Writing, R.B. N.W.S. and K.M.A.; Visualization, R.B. C.-W.C. R.K. N.S.W. and K.M.A.; Supervision, M.H. Y.L. G.B.M. G.R. J.I.W. S.R.K. D.J.D. N.W.S. and K.M.A.; Funding Acquisition, G.B.M. M.H. N.W.S. and K.M.A. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = aug,
day = "20",
doi = "10.1016/j.celrep.2019.07.084",
language = "English (US)",
volume = "28",
pages = "1971--1980.e8",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}