1. Academic Validation
  2. BRD4L cooperates with MYC to block local tumor invasion via suppression of S100A10

BRD4L cooperates with MYC to block local tumor invasion via suppression of S100A10

  • Cell Signal. 2024 Jul:119:111173. doi: 10.1016/j.cellsig.2024.111173.
Yongyi Ma 1 Nan Liu 2 Yu Shi 1 Shuyan Ma 1 Yingjun Wang 3 Wen Zheng 1 Rong Sun 4 Yihua Song 5 Miaomiao Chen 6 Lishuai Qu 7 Renfang Mao 8 Yihui Fan 9
Affiliations

Affiliations

  • 1 Department of Pathogenic Biology, School of Medicine, Nantong University, Nantong 226001, China; Laboratory of Medical Science, School of Medicine, Nantong University, Nantong 226001, China.
  • 2 Laboratory of Medical Science, School of Medicine, Nantong University, Nantong 226001, China; Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.
  • 3 Department of Pathophysiology, School of Medicine, Nantong University, Nantong 226001, China.
  • 4 Department of Pathogenic Biology, School of Medicine, Nantong University, Nantong 226001, China.
  • 5 Department of Stomatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.
  • 6 Laboratory of Medical Science, School of Medicine, Nantong University, Nantong 226001, China.
  • 7 Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. Electronic address: qulishuai1121@163.com.
  • 8 Department of Pathophysiology, School of Medicine, Nantong University, Nantong 226001, China. Electronic address: maorenfang@ntu.edu.cn.
  • 9 Department of Pathogenic Biology, School of Medicine, Nantong University, Nantong 226001, China; Laboratory of Medical Science, School of Medicine, Nantong University, Nantong 226001, China. Electronic address: fanyihui@ntu.edu.cn.
Abstract

Targeted therapy based on BRD4 and MYC shows promise due to their well-researched oncogenic functions in Cancer, but their tumor-suppressive roles are less understood. In this study, we employ a systematic approach to delete exons that encode the low-complexity domain (LCD) of BRD4L in cells by using CRISPR-Cas9. In particular, the deletion of exon 14 (BRD4-E14) results in cellular morphological changes towards spindle-shaped and loosely packed. BRD4-E14 deficient cells show increased cell migration and reduced cell adhesion. The expression of S100A10 was significantly increased in cells lacking E14. BRD4L binds with MYC via the E14-encoded region of the LCD to inhibit the expression of S100A10. In Cancer tissues, there is a positive correlation between BRD4 and MYC, while both of these proteins are negatively associated with S100A10 expression. Finally, knocking out the BRD4-E14 region or MYC promotes tumor growth in vivo. Together, these data support a tumor-suppressive role of BRD4L and MYC in some contexts. This discovery emphasizes the significance of a discreetly design and precise patient recruitment in clinical trials that testing Cancer therapy based BRD4 and MYC.

Keywords

BRD4L; Cell adhesion; MYC; S100A10; Tumor development.

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