SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway.
SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway.
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前列腺癌（PCa）转移的机制仍然知之甚少，已知有几种癌基因可以调节这一过程。然而，Spalt 样转录因子 4 (SALL4) 在 PCa 转移中的作用仍不清楚。我们进行了 RNA 测序，以比较 7 个局部 PCa 组织和 6 个转移性 PCa 组织的 mRNA 表达谱。然后在局部 PCa 和转移性 PCa 中鉴定并比较 SALL4。通过免疫组织化学研究、qRT-PCR 和蛋白质印迹分析 PCa 患者和细胞系中 SALL4 的表达。在 TCGA 数据库和我们的 68 个临床样本中进一步探讨了 SALL4 表达及其与临床特征和预后的相关性。随后，我们敲低了 DU145 和 PC3 细胞中的 SALL4，并进行了一系列功能测定，以探讨 SALL4 对 PCa 进展的影响。最后，通过Western blot检测SALL4和MAPK通路核心成分的蛋白水平，并用PD0325901处理细胞，观察增殖和转移情况。在转移性 PCa 中发现 SALL4 的表达显着高于局部 PCa。此外，在 TCGA 数据库和我们的临床样本中，高 SALL4 表达与高病理 T 分期、N 分期、Gleason 评分以及较差的无病生存率显着相关。功能研究表明，敲除 DU145 和 PC3 中的 SALL4 可抑制增殖、迁移和血管生成。此外，敲低 DU145 和 PC3 中的 SALL4 后，ERK 和 P38 蛋白磷酸化显着降低，表明 MAPK 信号通路失活。最后，PD0325901处理后DU145和PC3细胞的增殖和迁移能力显着下降。 SALL4 可以预测不良结果，并且与 PCa 进展密切相关，这表明 SALL4 可能是 PCa 的一个有前途的预后标志物和潜在的治疗靶点。
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. 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. 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 angiogenesis. Furthermore, the ERK and P38 protein phosphorylation significantly reduced after knockdown of SALL4 in DU145 and PC3, indicating the inactivation of the MAPK signaling pathway. Finally, the proliferation and migration ability of DU145 and PC3 cells were significantly decreased after PD0325901 treatment. SALL4 predicts unfavorable outcome and is closely associated with PCa progression, suggesting that SALL4 may be a promising prognostic marker and potential therapeutic target for PCa.
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影响因子：
11.2
作者：
Abdul Pari AA;Singhal M;Hübers C;Mogler C;Schieb B;Gampp A;Gengenbacher N;Reynolds LE;Terhardt D;Géraud C;Utikal J;Thomas M;Goerdt S;Hodivala-Dilke KM;Augustin HG;Felcht M
通讯作者：
Felcht M
癌细胞标记物的共表达SALL4/ALDH1A1与浆液性卵巢癌患者的肿瘤侵袭性和生存率差有关。
影响因子：
4
作者：
Sharbatoghli M;Shamshiripour P;Fattahi F;Kalantari E;Habibi Shams Z;Panahi M;Totonchi M;Asadi-Lari Z;Madjd Z;Saeednejad Zanjani L
通讯作者：
Saeednejad Zanjani L
影响因子：
9.2
作者：
Peng, Shengmeng;Chen, Xu;Huang, Chaoyun;Yang, Chenwei;Situ, Minyi;Zhou, Qianghua;Ling, Yihong;Huang, Hao;Huang, Ming;Zhang, Yangjie;Cheng, Liang;Zhang, Qiang;Guo, Zhenghui;Lai, Yiming;Huang, Jian
通讯作者：
Huang, Jian
影响因子：
254.7
作者：
Miller, Kimberly D.;Nogueira, Leticia;Siegel, Rebecca L.
通讯作者：
Siegel, Rebecca L.
影响因子：
8.9
作者：
Gong, Guiyi;Kam, Hiotong;Lee, Simon Ming-yuen
通讯作者：
Lee, Simon Ming-yuen