2. Academic Validation
  3. 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: [email protected].
  • 8 Department of Pathophysiology, School of Medicine, Nantong University, Nantong 226001, China. Electronic address: [email protected].
  • 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: [email protected].
PMID: 38604343 DOI: 10.1016/j.cellsig.2024.111173
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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