Work

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

Year: 2026

Type: article

Abstract: • Transcription factor VAX2 is frequently upregulated in colorectal cancer (CRC) internal sample set and external cohorts and cell lines. • VAX2 expression is observably correlated with tumor invasiveness and AJCC stage of tumors in CRC. • Decreased expression of VAX2 functionally inhibits the proliferation and facilitates the apoptosis of CRC cells and vice versa. • 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, decreased expression of SERPINE1 or oral administration of SERPINE1 inhibitor Tiplaxtinin attenuates VAX2-enhanced proliferation capacity. • Consistent with analysis of TCGA-CRC, positive correlation can be detected between VAX2 and SERPINE1 in fresh CRC samples. 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.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2026.102703