The VAX2-SERPINE1 axis modulates colorectal cancer cell proliferation and apoptosis through WNT/beta-catenin signaling

  • Transl Oncol. 2026 Apr:66:102703. doi: 10.1016/j.tranon.2026.102703.
Jieming Zhang  1 ,  Guangnan Liu  1 ,  Siyang Peng  1 ,  Yidong Chen  1 ,  Yanci Xie  1 ,  Yuting Lei  1 ,  Jieke Wu  1 ,  Xiaodong Huang  1 ,  Xiangyang Wei  1 ,  Linjie Hong  1 ,  Ping Yang  1 ,  Ying Peng  1 ,  Weimei Tang  1 ,  Xiaosheng Wu  1 ,  Aimin Li  1 ,  Side Liu  1 ,  Xinpeng Shi  2 ,  Jing Xiong  1 ,  Jide Wang  3
Affiliations
  • 1. Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 2. Department of Radiation Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, China.
  • 3. Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
PMID: 41691849 DOI: 10.1016/j.tranon.2026.102703
Abstract

Transcription factors (TFs) involve in colorectal Cancer (CRC). However, the function and mechanism of VAX2 in the development of CRC remain barely known. In the present study, we observed that transcription factor VAX2 is frequently upregulated in CRC internal sample set and external tissue microarray and cell lines. High VAX2 expression is observably correlated with tumor invasiveness and AJCC stage of tumors in CRC. Furthermore, decreased expression of VAX2 functionally inhibits the proliferation and facilitates the Apoptosis of CRC cells and vice versa. Mechanistically, VAX2 involves in Wnt/beta-catenin signaling through facilitating the nucleus accumulation of beta-catenin and VAX2 specifically binds to the promoter and trigger the transcription of SERPINE1. SERPINE1 overexpression significantly reverses the suppression of malignant behavior and nucleus accumulation of beta-catenin induced by VAX2 knockdown in vitro. In vivo, both the knockdown of SERPINE1 and the oral administration of its inhibitor Tiplaxtinin consistently attenuated the VAX2-enhanced proliferative capacity. Consistent with analysis of TCGA-CRC, positive correlation can be detected between VAX2 and SERPINE1 in fresh CRC samples. Thus, VAX2-SERPINE1 axis participate in CRC progression and work as a potential target against CRC.

Keywords
Beta-catenin; Colorectal cancer; SERPINE1; VAX2.
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