Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ccr.2010.10.021
Title: B55β-Associated PP2A Complex Controls PDK1-Directed Myc signaling and modulates rapamycin sensitivity in colorectal cancer
Authors: Tan, J.
Lee, P.L.
Li, Z.
Jiang, X.
Lim, Y.C.
Hooi, S.C.
Yu, Q. 
Issue Date: 16-Nov-2010
Citation: Tan, J., Lee, P.L., Li, Z., Jiang, X., Lim, Y.C., Hooi, S.C., Yu, Q. (2010-11-16). B55β-Associated PP2A Complex Controls PDK1-Directed Myc signaling and modulates rapamycin sensitivity in colorectal cancer. Cancer Cell 18 (5) : 459-471. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ccr.2010.10.021
Abstract: The PP2A serine/threonine protein phosphatase serves as a critical cellular regulator of cell growth, proliferation, and survival. However, how this pathway is altered in human cancer to confer growth advantage is largely unknown. Here, we show that PPP2R2B, encoding the B55β regulatory subunit of the PP2A complex, is epigenetically inactivated by DNA hypermethylation in colorectal cancer. B55β-associated PP2A interacts with PDK1 and modulates its activity toward Myc phosphorylation. On loss of PPP2R2B, mTORC1 inhibitor rapamycin triggers a compensatory Myc phosphorylation in PDK1-dependent, but PI3K and AKT-independent manner, resulting in resistance. Reexpression of PPP2R2B, genetic ablation of PDK1 or pharmacologic inhibition of PDK1 abrogates the rapamycin-induced Myc phosphorylation, leading to rapamycin sensitization. Thus, PP2A-B55β antagonizes PDK1-Myc signaling and modulates rapamycin sensitivity. © 2010 Elsevier Inc.
Source Title: Cancer Cell
URI: http://scholarbank.nus.edu.sg/handle/10635/116237
ISSN: 15356108
DOI: 10.1016/j.ccr.2010.10.021
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