PKM2 is not required for colon cancer initiated by APC loss.
PKM2 is not required for colon cancer initiated by APC loss.
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DOI：
10.1186/s40170-017-0172-1
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发表时间：
2017
影响因子：
5.9
通讯作者：
Vander Heiden MG
中科院分区：
文献类型：
--
作者：
Lau AN;Israelsen WJ;Roper J;Sinnamon MJ;Georgeon L;Dayton TL;Hillis AL;Yilmaz OH;Di Vizio D;Hung KE;Vander Heiden MG
癌细胞表达糖酵解酶丙酮酸激酶(PKM2)的M2亚型。一些癌症并不需要PKM2的表达，而PKM2的缺失可以促进癌症的进展；然而，据报道，在其他肿瘤环境中，PKM2是必不可少的，包括被提议的在β-连环蛋白核转位中的非代谢作用。PKM2在结肠癌中表达，在结肠癌中，APC抑癌基因的缺失会导致β-连环蛋白的核转位和规范的Wnt信号通路的异常激活。在结肠癌的情况下是否需要PKM2还没有被研究。在携带条件APC和PKM2等位基因的小鼠中诱导结肠肿瘤形成，并通过连续结肠镜检查肿瘤进展。PKM2缺失对总存活率、发生肿瘤的小鼠数量或每只动物发生肿瘤的数量没有影响。免疫组织化学分析显示PKM2在野生型肿瘤中表达，而在PKM2条件性小鼠肿瘤中PKM2表达预期丢失。PKM2缺失导致丙酮酸激酶M1的表达，但不影响核β-连环蛋白的染色。这些发现与肿瘤生长和激活Wnt信号是一致的，尽管在该模型中PKM2丢失。我们还发现，在很大一部分人类结肠癌中，PKM2的表达水平非常低或检测不到。蛋白酪氨酸激酶M2不是缺乏蛋白原的结肠癌所必需的，也不是β-连环蛋白在蛋白原缺失的肿瘤细胞中的核转位所必需的。这些发现表明，PKM2的表达不是结肠癌形成或发展所必需的。本文的在线版本(10.1186/s40170170.172-1)包含补充材料，可供授权用户使用。
Cancer cells express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2). PKM2 expression is not required for some cancers, and PKM2 loss can promote cancer progression; however, PKM2 has been reported to be essential in other tumor contexts, including a proposed non-metabolic role in β-catenin nuclear translocation. PKM2 is expressed in colon cancers where loss of the Apc tumor suppressor results in β-catenin nuclear translocation and aberrant activation of the canonical Wnt signaling pathway. Whether PKM2 is required in this colon cancer context has not been investigated. Colon tumorigenesis was induced in mice harboring conditional Apc and Pkm2 alleles, and tumor progression was monitored by serial colonoscopy. PKM2 deletion had no effect on overall survival, the number of mice that developed tumors, or the number of tumors that developed per animal. Immunohistochemical analysis demonstrated PKM2 expression in wild-type tumors and the expected loss of PKM2 expression in tumors from Pkm2 conditional mice. Loss of PKM2 resulted in pyruvate kinase M1 expression but had no effect on nuclear β-catenin staining. These findings are consistent with tumor growth and activated Wnt signaling despite PKM2 loss in this model. We also found a large fraction of human colon cancers had very low or undetectable levels of PKM2 expression. PKM2 is not required for Apc-deficient colon cancer or for nuclear translocation of β-catenin in Apc-null tumor cells. These findings suggest that PKM2 expression is not required for colon tumor formation or progression. The online version of this article (10.1186/s40170-017-0172-1) contains supplementary material, which is available to authorized users.
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影响因子：
51.1
作者：
Moroni, M;Veronese, S;Bardelli, A
通讯作者：
Bardelli, A
影响因子：
11.5
作者：
Martin, Eric S.;Belmont, Peter J.;Hung, Kenneth E.
通讯作者：
Hung, Kenneth E.
丙酮酸激酶 M2 通过调节 STAT3 信号传导促进结肠癌细胞迁移
影响因子：
4.8
作者：
Yang, Peng;Li, Zongwei;Li, Zhuoyu
通讯作者：
Li, Zhuoyu
影响因子：
7.3
作者：
Gui, Dan Y.;Lewis, Caroline A.;Vander Heiden, Matthew G.
通讯作者：
Vander Heiden, Matthew G.
丙酮酸激酶M2激活剂促进四聚体形成并抑制肿瘤发生。
影响因子：
14.8
作者：
Anastasiou, Dimitrios;Yu, Yimin;Israelsen, William J.;Jiang, Jian-Kang;Boxer, Matthew B.;Hong, Bum Soo;Tempel, Wolfram;Dimov, Svetoslav;Shen, Min;Jha, Abhishek;Yang, Hua;Mattaini, Katherine R.;Metallo, Christian M.;Fiske, Brian P.;Courtney, Kevin D.;Malstrom, Scott;Khan, Tahsin M.;Kung, Charles;Skoumbourdis, Amanda P.;Veith, Henrike;Southall, Noel;Walsh, Martin J.;Brimacombe, Kyle R.;Leister, William;Lunt, Sophia Y.;Johnson, Zachary R.;Yen, Katharine E.;Kunii, Kaiko;Davidson, Shawn M.;Christofk, Heather R.;Austin, Christopher P.;Inglese, James;Harris, Marian H.;Asara, John M.;Stephanopoulos, Gregory;Salituro, Francesco G.;Jin, Shengfang;Dang, Lenny;Auld, Douglas S.;Park, Hee-Won;Cantley, Lewis C.;Thomas, Craig J.;Heiden, Matthew G. Vander
通讯作者：
Heiden, Matthew G. Vander