2. Academic Validation
  3. Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer

Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer

  • Oncogenesis. 2023 Feb 4;12(1):3. doi: 10.1038/s41389-023-00448-4.
Weigang Dai # 1 2,  Yinan Liu # 1 2 3,  Tianhao Zhang 1 2,  Zhixin Huang 1 2 3,  Xiang Xu 1 2,  Zeyu Zhao 1 2,  Jianqiu Liu 1 2,  Ertao Zhai 4 5,  Shirong Cai 6 7,  Jianhui Chen 8 9
Affiliations

Affiliations

  • 1 Division of Gastrointestinal Surgery Center, the First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China.
  • 2 Gastric Cancer Center, Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China.
  • 3 Laboratory of Surgery, the First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China.
  • 4 Division of Gastrointestinal Surgery Center, the First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China. zhaiert@mail2.sysu.edu.cn.
  • 5 Gastric Cancer Center, Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China. zhaiert@mail2.sysu.edu.cn.
  • 6 Division of Gastrointestinal Surgery Center, the First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China. caishr@mail.sysu.edu.cn.
  • 7 Gastric Cancer Center, Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China. caishr@mail.sysu.edu.cn.
  • 8 Division of Gastrointestinal Surgery Center, the First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China. chenjh45@mail.sysu.edu.cn.
  • 9 Gastric Cancer Center, Sun Yat-sen University, 510080, Guangzhou, Guangdong, P. R. China. chenjh45@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 36739270 DOI: 10.1038/s41389-023-00448-4
Abstract

PBX1 is a transcription factor that regulates a variety of genes, involved in intracellular lipid metabolism, cell proliferation, and other pathways. The promoting and inhibiting function of PBX1 in various Cancer types was extensively discussed, however, there have been no studies on PBX1 proteins in colorectal Cancer (CRC). This study aimed to reveal the anti-tumor function of PBX1 in CRC and the underlying molecular mechanism. Bioinformatics analysis revealed that PBX1 is downregulated in CRC, indicating that is a potential antioncogene in CRC. Overexpression of PBX1 suppresses tumor growth and metastasis in vitro and in vivo. Mechanistically, we found that PBX1 acted as a transcription factor that suppressed DCDC2 expression and inhibited spindle function. Moreover, the PBX1-DCDC2 axis controlled the Wnt pathway in CRC cells. Overexpression of DCDC2 restored CRC proliferation, metastasis abilities and Wnt pathway. In conclusion, this study suggests that PBX1 acts as a transcription factor to suppress DCDC2 expression and inhibit cell proliferation and metastasis by disrupting spindle function and the Wnt pathway in CRC.

Figures
Products