MSRA公司
生物
巴基斯坦卢比
蛋氨酸
胰腺癌
转移
癌症研究
丙酮酸激酶
细胞生物学
生物化学
新陈代谢
癌症
糖酵解
氨基酸
遗传学
作者
Dan He,Huijin Feng,Belen Sundberg,Jun Yang,Justin L. Powers,Alec H. Christian,John E. Wilkinson,Cian Monnin,Daina Avizonis,Craig J. Thomas,Richard A. Friedman,Michael D. Kluger,Michael A. Hollingsworth,Paul M. Grandgenett,Kelsey Klute,F. Dean Toste,Christopher J. Chang,Iok In Christine Chio
出处
期刊:Molecular Cell
[Elsevier]
日期:2022-08-01
卷期号:82 (16): 3045-3060.e11
被引量:22
标识
DOI:10.1016/j.molcel.2022.06.005
摘要
Cancer mortality is primarily a consequence of its metastatic spread. Here, we report that methionine sulfoxide reductase A (MSRA), which can reduce oxidized methionine residues, acts as a suppressor of pancreatic ductal adenocarcinoma (PDA) metastasis. MSRA expression is decreased in the metastatic tumors of PDA patients, whereas MSRA loss in primary PDA cells promotes migration and invasion. Chemoproteomic profiling of pancreatic organoids revealed that MSRA loss results in the selective oxidation of a methionine residue (M239) in pyruvate kinase M2 (PKM2). Moreover, M239 oxidation sustains PKM2 in an active tetrameric state to promote respiration, migration, and metastasis, whereas pharmacological activation of PKM2 increases cell migration and metastasis in vivo. These results demonstrate that methionine residues can act as reversible redox switches governing distinct signaling outcomes and that the MSRA-PKM2 axis serves as a regulatory nexus between redox biology and cancer metabolism to control tumor metastasis.
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