2. Academic Validation
  3. 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

  • Cell Death Dis. 2023 Oct 16;14(10):682. doi: 10.1038/s41419-023-06200-5.
Bai Cui # 1,  Bin He # 1 2,  Yanping Huang # 3,  Cenxin Wang # 1,  Huandong Luo 1,  Jinxin Lu 1,  Keyu Su 1,  Xiaoyu Zhang 1,  Yuanyuan Luo 4,  Zhuoran Zhao 1,  Yuqing Yang 1,  Yunkun Zhang 5,  Fan An 1,  Hong Wang 6,  Eric W-F Lam 7,  Keith W Kelley 8,  Ling Wang 9,  Quentin Liu 10 11,  Fei Peng 12
Affiliations

Affiliations

  • 1 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • 2 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
  • 3 Department of Oncology, the First Affiliated Hospital of Dalian Medical University, Dalian, China.
  • 4 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
  • 5 Department of Pathology, The Second Hospital of Dalian Medical University, Dalian, China.
  • 6 Department of Orthopaedics, The Central Hospital of Dalian University of Technology, Dalian, China.
  • 7 Department of Surgery and Cancer, Imperial College London, London, UK.
  • 8 Department of Pathology, College of Medicine and Department of Animal Sciences, College of ACES, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
  • 9 Department of Oncology, the First Affiliated Hospital of Dalian Medical University, Dalian, China. [email protected].
  • 10 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. [email protected].
  • 11 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 12 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. [email protected].
  • # Contributed equally.
PMID: 37845207 DOI: 10.1038/s41419-023-06200-5
Abstract

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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