journal article·2024-10Open access

Polyamine Anabolism Promotes Chemotherapy‐Induced Breast Cancer Stem Cell Enrichment

Guangyu Ji, Jia Liu, Zhiqun Zhao, Jie Lan, You Yang, Zheng Wang, Huijing Feng, Kai Ji, Xiaofeng Jiang, Huize Xia, Guangyao Wei, Yajing Zhang, Yuhong Zhang, Xinlong Du, Yawen Wang, Yuanyuan Yang, Zhaojian Liu, Kai Zhang, Qi Mei, Rong Sun, Haiquan Lu

Advanced Science· Volume 11· Issue 40

Abstract

Abstract Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA‐based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy‐induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF‐1 in response to chemotherapy. Genetic inhibition of HIF‐1‐controlled polyamine anabolism blocks chemotherapy‐induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF‐1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy‐induced HIF‐1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment.
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Research context

OpenAlex topics: Polyamine Metabolism and Applications · Cancer Cells and Metastasis · Pancreatic function and diabetes

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

The Second Hospital and Advanced Medical Research Institute Cheeloo College of Medicine Shandong University Jinan 250012 China

School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 China

Department of Radiation Oncology Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China

Department of Pediatrics (Children Hematological Oncology) Birth Defects and Childhood Hematological Oncology Laboratory The Affiliated Hospital of Southwest Medical University Sichuan Clinical Research Center for Birth Defects Luzhou 646000 China

Department of Urology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan 250021 China

Cancer Center, Shanxi Bethune Hospital Shanxi Academy of Medical Sciences Tongji Shanxi Hospital Third Hospital of Shanxi Medical University Taiyuan 030032 China

Shandong Helix Matrix Data Technology Jinan 250014 China

Youth League Committee Qilu Hospital Shandong University Jinan 250012 China

Department of Breast Surgery, General Surgery Qilu Hospital Shandong University Jinan 250012 China

Shandong Artificial Intelligence Institute Qilu University of Technology (Shandong Academy of Sciences) Jinan 250399 China

Department of Oncology, Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430000 China

Key Laboratory for Experimental Teratology of the Ministry of Education Cheeloo College of Medicine Shandong University Jinan 250012 China

Center for Reproductive Medicine Shandong University Jinan 250001 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Shandong Province

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