2. Academic Validation
  3. BTB domain and CNC homolog 1 promotes glioma invasion mainly through regulating extracellular matrix and increases ferroptosis sensitivity

BTB domain and CNC homolog 1 promotes glioma invasion mainly through regulating extracellular matrix and increases ferroptosis sensitivity

  • Biochim Biophys Acta Mol Basis Dis. 2022 Dec 1;1868(12):166554. doi: 10.1016/j.bbadis.2022.166554.
Zixiang Cong 1,  Feng Yuan 1,  Handong Wang 2,  Xiangming Cai 3,  Junhao Zhu 1,  Ting Tang 1,  Li Zhang 1,  Yanling Han 1,  Chiyuan Ma 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
  • 2 Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; Department of Neurosurgery, Benq Medical Center, Nanjing Medical University, Nanjing 210002, China. Electronic address: [email protected].
  • 3 School of Medicine, Southeast University, Dingjiaqiao No. 87, Nanjing, 210000, Jiangsu, China.
  • 4 Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China. Electronic address: [email protected].
PMID: 36181980 DOI: 10.1016/j.bbadis.2022.166554
Abstract

BTB Domain and CNC Homolog 1 (Bach1) has been implicated in Cancer progression, particularly in invasion, but little is unknown about its effect on glioma. Here, we confirmed that highly expressed Bach1 prominently promoted glioma invasion. Similar to the reported mechanisms in other tumors, Bach1 upregulation was also correlated with epithelial mesenchymal transition (EMT) in glioma cells. More importantly, proteomic analysis indicated that the main mechanism of Bach1 promoting invasion in glioma involved extracellular matrix (ECM). We further found thatBach1 upregulation was associated with the multiple mechanisms of ECM remodeling in glioma, including increasing the expression and deposition of ECM components, activating TGFBR2-smad2/3 signaling, promoting invadopodia formation and inducing the expression and secretion of MMP2. Meanwhile, Bach1 overexpression increased Ferroptosis sensitivity in glioma cells. The Ferroptosis inducer (sulfasalazine) obviously suppressed the gliomas with Bach1 upregulation in vitro and in vivo. Overall, Bach1 has a two-faced role in glioma. Highly expressed Bach1 promotes glioma invasion. Conversely, Bach1 upregulation is also a potential indicator of the sensitivity of Ferroptosis inducers.

Keywords

Bach1; Extracellular matrix (ECM); Ferroptosis; Glioma; Invadopodia.

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