Disheveled3 enhanced EMT and cancer stem-like cells properties via Wnt/β-catenin/c-Myc/SOX2 pathway in colorectal cancer

作者：Zhengguang Li, Zhirong Yang, Wei Liu, Wanglong Zhu, Lan Yin, Zhenyu Han, Yu Xian, Jie Wen, Hualong Tang, Xinyue Lin, Yuhan Yang, Jingyi Wang, Kun Zhang · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04120-8 · 被引用次数：55 · 研究领域：Cancer Cells and Metastasis、Wnt/β-catenin signaling in development and cancer、Epigenetics and DNA Methylation

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis and drug-resistance. Disheveled3 (DVL3) is involved in malignant behaviors of cancer. However, the role and potential mechanism of DVL3 remain elusive in EMT and CSLCs of colorectal cancer (CRC). METHODS: UALCAN and PrognoScan databases were employed to evaluate DVL3 expression in CRC tissues and its correlation with CRC prognosis, respectively. Transwell, sphere formation and CCK8 assay were used to assess metastasis, stemness and drug sensitivity of CRC cells, respectively. Western blotting and dual luciferase assay were performed to analyze the protein expression and Wnt/β-catenin activation, respectively. Lentiviral transfection was used to construct the stable cell lines. Animal studies were performed to analyze the effect of silencing DVL3 on tumorigenicity and metastasis of CRC cells in vivo. RESULTS: DVL3 was overexpressed in CRC tissues and several CRC cell lines. DVL3 expression was also higher in CRC tissues with lymph node metastasis than tumor tissues without metastasis, and correlated with poor prognosis of CRC patients. DVL3 positively regulated the abilities of migration, invasion and EMT-like molecular changes in CRC cells. Moreover, DVL3 promoted CSLCs properties and multidrug resistance. We further identified that Wnt/β-catenin was crucial for DVL3-mediated EMT, stemness and SOX2 expression, while silencing SOX2 inhibited DVL3-medi...