SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway

作者：Jie Zhou, Shengmeng Peng, Huiyang Fan, Jin Li, Zean Li, Ganping Wang, Lexiang Zeng, Zhenghui Guo, Yiming Lai, Hai Huang · 发表于：Cancer Medicine · 年份：2023 · DOI：10.1002/cam4.5998 · 被引用次数：14 · 研究领域：Renal and related cancers、Wnt/β-catenin signaling in development and cancer、Kruppel-like factors research

BACKGROUND: The mechanism involved in prostate cancer (PCa) metastasis is still poorly understood, and several oncogenes are known to regulate this process. However, the role of spalt-like transcription factor 4 (SALL4) in PCa metastasis remains unclear. METHODS: We performed RNA-sequencing to compare the mRNA expression profiles of seven localized PCa tissues and six metastatic PCa tissues. SALL4 was then identified and compared in the localized PCa and metastatic PCa. Immunohistochemical studies, qRT-PCR, and Western blot were performed to analyze the expression of SALL4 in PCa patients and cell lines. SALL4 expression and its relevance to clinical traits and prognosis were further explored in the TCGA database and in our 68 clinical samples. Subsequently, we knocked down SALL4 in DU145 and PC3 cells and performed a series of functional assays to explore the effect of SALL4 on PCa progression. Finally, protein levels of SALL4 and core components of the MAPK pathway were measured by Western blot, and cells were treated with PD0325901 to observe proliferation and metastasis. RESULTS: Significantly higher expression of SALL4 was found in metastatic PCa than in localized PCa. In addition, high SALL4 expression was significantly associated with high pathological T stage, N stage, Gleason score, and poor disease-free survival in TCGA database and in our clinical samples. Functional studies indicated that knockdown of SALL4 in DU145 and PC3 inhibited proliferation, migration, and ...