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.

PBX1是一种调控多种基因的转录因子，参与细胞内脂质代谢、细胞增殖等通路。广泛讨论了 PBX1 在各种癌症类型中的促进和抑制功能，但是，还没有关于 PBX1 蛋白在结直肠癌 (CRC) 中的研究。本研究旨在揭示PBX1在CRC中的抗肿瘤作用及其分子机制。生物信息学分析显示 PBX1 在 CRC 中下调，表明它是 CRC 中潜在的抗癌基因。PBX1 的过表达在体外和体内抑制肿瘤生长和转移。从机制上讲，我们发现 PBX1 充当抑制DCDC2的转录因子表达和抑制纺锤体功能。此外，PBX1-DCDC2 轴控制 CRC 细胞中的 Wnt 通路。DCDC2 的过表达恢复了 CRC 增殖、转移能力和 Wnt 通路。总之，本研究表明 PBX1 作为转录因子通过破坏 CRC 中的纺锤体功能和 Wnt 通路来抑制 DCDC2 表达并抑制细胞增殖和转移。