2. Academic Validation
  3. Cancer-associated adipocyte-derived G-CSF promotes breast cancer malignancy via Stat3 signaling

Cancer-associated adipocyte-derived G-CSF promotes breast cancer malignancy via Stat3 signaling

  • J Mol Cell Biol. 2020 Sep 1;12(9):723-737. doi: 10.1093/jmcb/mjaa016.
Li Liu 1,  Yudong Wu 2,  Cheng Zhang 1,  Chong Zhou 1,  Yining Li 1,  Yi Zeng 1,  Chunbo Zhang 3,  Rong Li 4,  Daya Luo 1,  Lieliang Wang 2,  Long Zhang 5,  Shuo Tu 1,  Huan Deng 6,  Shiwen Luo 7,  Ye-Guang Chen 8,  Xiangyang Xiong 1,  Xiaohua Yan 1 9 10
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China.
  • 2 Department of Breast Surgery, Jiangxi Provincial Cancer Hospital, Nanchang 330029, China.
  • 3 School of Pharmacy, Nanchang University, Nanchang 330006, China.
  • 4 School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China.
  • 5 Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
  • 6 Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330003, China.
  • 7 Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
  • 8 The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 9 Institute of Biomedical Sciences, Nanchang University Medical College, Nanchang 330031, China.
  • 10 Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology, Nanchang University Medical College, Nanchang 330006, China.
PMID: 32242230 DOI: 10.1093/jmcb/mjaa016
Abstract

Adipocyte is the most predominant cell type in the tumor microenvironment of breast Cancer and plays a pivotal role in Cancer progression, yet the underlying mechanisms and functional mediators remain elusive. We isolated primary preadipocytes from mammary fat pads of human breast Cancer patients and generated mature adipocytes and cancer-associated adipocytes (CAAs) in vitro. The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing. One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor (G-CSF). Treatment with recombinant human G-CSF protein or stable expression of human G-CSF in triple-negative breast Cancer (TNBC) cell lines enhanced epithelial-mesenchymal transition, migration, and invasion of Cancer cells, by activating STAT3. Accordantly, targeting G-CSF/STAT3 signaling with G-CSF-neutralizing antibody, a chemical inhibitor, or siRNAs for STAT3 could all abrogate CAA- or G-CSF-induced migration and invasion of breast Cancer cells. The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells. Furthermore, in human breast Cancer tissues, elevated G-CSF expression in adipocytes is well correlated with activated STAT3 signal in Cancer cells. Together, our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAA-derived G-CSF.

Keywords

G-CSF; cancer-associated adipocyte; epithelial–mesenchymal transition (EMT); migration and invasion; triple-negative breast cancer (TNBC).

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