Pyrroline-5-carboxylate reductase 1 reprograms proline metabolism to drive breast cancer stemness under psychological stress.
Pyrroline-5-carboxylate reductase 1 reprograms proline metabolism to drive breast cancer stemness under psychological stress.
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DOI：
10.1038/s41419-023-06200-5
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发表时间：
2023-10-16
影响因子：
9
通讯作者：
Peng, Fei
中科院分区：
文献类型：
--
作者：
Cui, Bai;He, Bin;Huang, Yanping;Wang, Cenxin;Luo, Huandong;Lu, Jinxin;Su, Keyu;Zhang, Xiaoyu;Luo, Yuanyuan;Zhao, Zhuoran;Yang, Yuqing;Zhang, Yunkun;An, Fan;Wang, Hong;Lam, Eric W. -F.;Kelley, Keith W.;Wang, Ling;Liu, Quentin;Peng, Fei
癌症干细胞（Cancer stem-like cells, CSCs）参与癌症转移、耐药和肿瘤复发，但氨基酸代谢如何促进CSC维持尚不清楚。在这里，我们发现脯氨酸合成酶PYCR1对乳腺癌的干细胞和肿瘤生长至关重要。从机制上讲，pycr1合成的脯氨酸激活cGMP-PKG信号以增强癌症茎样性状。重要的是，cGMP-PKG信号介导心理应激诱导的癌症干细胞样表型和肿瘤发生。消融PYCR1可显著逆转心理应激诱导的脯氨酸合成、cGMP-PKG信号激活和癌症进展。临床上，PYCR1和cGMP-PKG信号成分在乳腺肿瘤标本中高表达，导致乳腺癌患者生存率较低。针对脯氨酸代谢或cGMP-PKG信号通路为乳腺癌患者心理应激提供了潜在的治疗策略。总的来说，我们的发现揭示了pycr1增强的脯氨酸合成在维持乳腺癌干细胞中发挥着关键作用。
Cancer stem-like cells (CSCs) contribute to cancer metastasis, drug resistance and tumor relapse, yet how amino acid metabolism promotes CSC maintenance remains exclusive. Here, we identify that proline synthetase PYCR1 is critical for breast cancer stemness and tumor growth. Mechanistically, PYCR1-synthesized proline activates cGMP-PKG signaling to enhance cancer stem-like traits. Importantly, cGMP-PKG signaling mediates psychological stress-induced cancer stem-like phenotypes and tumorigenesis. Ablation of PYCR1 markedly reverses psychological stress-induced proline synthesis, cGMP-PKG signaling activation and cancer progression. Clinically, PYCR1 and cGMP-PKG signaling components are highly expressed in breast tumor specimens, conferring poor survival in breast cancer patients. Targeting proline metabolism or cGMP-PKG signaling pathway provides a potential therapeutic strategy for breast patients undergoing psychological stress. Collectively, our findings unveil that PYCR1-enhanced proline synthesis displays a critical role in maintaining breast cancer stemness.
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影响因子：
6.4
作者：
Banerjee J;Papu John AM;Schuller HM
通讯作者：
Schuller HM
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影响因子：
15.1
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Fang, Erhu;Wang, Xiaojing;Tong, Qiangsong
通讯作者：
Tong, Qiangsong
脯氨酸代谢在癌症中的作用。
影响因子：
7
作者：
Burke L;Guterman I;Palacios Gallego R;Britton RG;Burschowsky D;Tufarelli C;Rufini A
通讯作者：
Rufini A
影响因子：
16.6
作者：
Elia I;Broekaert D;Christen S;Boon R;Radaelli E;Orth MF;Verfaillie C;Grünewald TGP;Fendt SM
通讯作者：
Fendt SM