HAUS1 Promotes Colorectal Cancer Progression by Activating CDCA8 Transcription Through the HAUS1-EZH2-E2F1 Axis.

Colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide, underscoring the need to identify new drivers of tumor progression. HAUS augmin-like complex subunit 1 (HAUS1), a component of the microtubule-augmin complex, has been implicated in mitotic spindle assembly; however, its clinical significance and mechanistic contribution to CRC are largely unknown. Here, we reported that HAUS1 was markedly upregulated in CRC tissues and cell lines, and its high expression correlated with lymphatic metastasis and poor patient prognosis. Functional experiments demonstrated that HAUS1 depletion significantly impaired CRC cell proliferation, migration, and tumor growth in vitro and in vivo. Mechanistically, transcriptomic profiling and integrative bioinformatic analyses identified CDCA8 as a key downstream effector of HAUS1. HAUS1 physically interacted with EZH2 and facilitated the recruitment of E2F1 to the CDCA8 promoter, thereby enhancing CDCA8 transcription through a methylation-independent HAUS1-EZH2-E2F1 axis. Disruption of CDCA8 abrogated the oncogenic effects induced by HAUS1 overexpression, confirming its essential role in HAUS1-driven tumor progression. Furthermore, HAUS1 was required for maintaining cancer stem-like properties, as HAUS1 silencing reduced stemness marker expression, impaired sphere formation, and decreased tumor-initiating cell frequency in vivo-effects that were reversed by CDCA8 restoration. Collectively, our findings identified HAUS1 as a clinically relevant oncogenic driver that promoted CRC progression and cancer stemness by transcriptionally activating CDCA8. Targeting the HAUS1-EZH2-E2F1-CDCA8 signaling axis might represent a promising therapeutic strategy for CRC.