@article{0ae80c2f9ecf44f3879e2ab266e7e7e1,
title = "XPKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells",
abstract = "The pyruvate kinase M2 isoform (PKM2) is expressed in cancer and plays a role in regulating anabolic metabolism. To determine whether PKM2 is required for tumor formation or growth, we generated mice with a conditional allele that abolishes PKM2 expression without disrupting PKM1 expression. PKM2 deletion accelerated mammary tumor formation in a Brca1-loss-driven model of breast cancer. PKM2 null tumors displayed heterogeneous PKM1 expression, with PKM1 found in nonproliferating tumor cells and no detectable pyruvate kinase expression in proliferating cells. This suggests that PKM2 is not necessary for tumor cell proliferation and implies that the inactive state of PKM2 is associated with the proliferating cell population within tumors, whereas nonproliferating tumor cells require active pyruvate kinase. Consistent with these findings, variable PKM2 expression and heterozygous PKM2 mutations are found in human tumors. These data suggest that regulation of PKM2 activity supports the different metabolic requirements of proliferating and nonproliferating tumor cells. PaperClip",
author = "Israelsen, {William J.} and Dayton, {Talya L.} and Davidson, {Shawn M.} and Fiske, {Brian P.} and Hosios, {Aaron M.} and Gary Bellinger and Jie Li and Yimin Yu and Mika Sasaki and Horner, {James W.} and Burga, {Laura N.} and Jianxin Xie and Jurczak, {Michael J.} and Depinho, {Ronald A.} and Clish, {Clary B.} and Tyler Jacks and Kibbey, {Richard G.} and Wulf, {Gerburg M.} and {Di Vizio}, Dolores and Mills, {Gordon B.} and Cantley, {Lewis C.} and {Vander Heiden}, {Matthew G.}",
note = "Funding Information: We thank Chu-Xia Deng for sharing the BRCA1 mouse model; Luigi Terracciano and Luigi Tornillo for providing the multitissue TMA; and Cynthia Clower, Sarah-Maria Fendt, Andrea J. Howell, Vivian M. Liu, Sophia Lunt, Katherine R. Mattaini, Benjamin A. Olenchock, and Kerry Pierce for technical assistance. Eric L. Bell provided advice and reagents. Denise G. Crowley, Michael Brown, and Kathleen S. Cormier assisted with histology. This work was supported, in part, by NIH grants R01CA168653, 5P01CA117969, P30CA147882, 5P30CA14051, 5K08CA136983, DK059635, R01DK092606, R00CA131472, and R01GM056203 and ADA grant 7-12-BS-09. R.A.D. and J.W.H. acknowledge support from the Belfer Foundation. M.G.V.H. acknowledges additional support from the Smith Family Foundation, the Burroughs Wellcome Fund, the Damon Runyon Cancer Research Foundation, and the Stern family. C.B.C. is a shareholder in Agios Pharmaceuticals. M.G.V.H. is a shareholder and Scientific Advisory Board member at Agios Pharmaceuticals. L.C.C. owns equity in and receives compensation from Agios Pharmaceuticals and serves on the Board of Directors and Scientific Advisory Board. ",
year = "2013",
month = oct,
day = "10",
doi = "10.1016/j.cell.2013.09.025",
language = "English (US)",
volume = "155",
pages = "397",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}