DACH1 antagonizes CXCL8 to repress tumorigenesis of lung adenocarcinoma and improve prognosis.
DACH1 antagonizes CXCL8 to repress tumorigenesis of lung adenocarcinoma and improve prognosis.
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DACH1拮抗CXCL8抑制肺腺癌肿瘤发生并改善预后
DOI：
10.1186/s13045-018-0597-1
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发表时间：
2018-04-10
影响因子：
28.5
通讯作者：
Wu K
中科院分区：
文献类型：
--
作者：
Liu Q;Li A;Yu S;Qin S;Han N;Pestell RG;Han X;Wu K
BackgroundC-X-C motif ligand 8 (CXCL8), known as a proinflammatory chemokine, exerts multiple effects on the proliferation, invasion, and migration of tumor cells via the autocrine or paracrine manner. Conversely, the human Dachshund homologue 1 (DACH1) is recognized as a tumor suppressor which retards the progression of various cancers. In prostate cancer, it has been demonstrated that DACH1 was negatively correlated with the expression of CXCL8 and able to antagonize the effects of CXCL8 on cellular migration. Herein, we explored the mechanisms by which DACH1 regulated the CXCL8 in non-small cell lung cancer (NSCLC).MethodsPublic microarray and Kaplan-Meier plotter datasets were analyzed. Blood serum samples from lung adenocarcinoma (ADC) patients were collected for enzyme-linked immunosorbent assay (ELISA) analysis. Immunohistochemical staining was conducted on tissue microarray. Cell lines with stable expression of DACH1 were established, and relative gene expression was measured by Western blot, ELISA, real-time PCR, and human cytokine array. Correspondingly, cell lines transfected with shDACH1 were established, and relative gene expression was measured by real-time PCR and immunofluorescence array. Functional studies were performed by transwell and xenograft mice models. Luciferase reporter gene assay was applied to measure the regulation of DACH1 on CXCL8.ResultsOur study indicated that CXCL8 both at the mRNA and protein level was associated with the high tumor burden of ADC. Correlational analyses in ADC cell lines and ADC tissues showed that DACH1 was inversely correlated with CXCL8. Meanwhile, patients with high DACH1 expression and low CXCL8 expression had prolonged time to death and recurrence. Moreover, we verified the inhibitory effects of DACH1 on CXCL8 both in vitro and in vivo. Mechanism studies proved that DACH1 transcriptionally repressed CXCL8 promoter activity through activator protein-1 (AP-1) and nuclear transcription factor-kappa B (NF-κB) sites.ConclusionsOur study proved that CXCL8 acted as an unfavorable factor promoting to tumor progression and poor prognosis of ADC, while DACH1 antagonized CXCL8 to provide a favorable survival of ADC patients. Double detection of DACH1 and CXCL8 may provide a precise information for further evaluating the prognosis of ADC patients.
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影响因子：
28.5
作者：
Li X;Wang S;Zhu R;Li H;Han Q;Zhao RC
通讯作者：
Zhao RC
影响因子：
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作者：
Dalmases A;González I;Menendez S;Arpí O;Corominas JM;Servitja S;Tusquets I;Chamizo C;Rincón R;Espinosa L;Bigas A;Eroles P;Furriol J;Lluch A;Rovira A;Albanell J;Rojo F
通讯作者：
Rojo F
影响因子：
11.2
作者：
Chen K;Wu K;Jiao X;Wang L;Ju X;Wang M;Di Sante G;Xu S;Wang Q;Li K;Sun X;Xu C;Li Z;Casimiro MC;Ertel A;Addya S;McCue PA;Lisanti MP;Wang C;Davis RJ;Mardon G;Pestell RG
通讯作者：
Pestell RG
肾小球病中 DACH1 表达降低与疾病进展和严重程度相关
影响因子：
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作者：
Liu, Qing-Quan;Zhou, Ya-Qun;Wu, Kong-Ming
通讯作者：
Wu, Kong-Ming
视网膜决定基因网络：从发育调节因子到癌症治疗靶点
影响因子：
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作者：
Kong D;Liu Y;Liu Q;Han N;Zhang C;Pestell RG;Wu K;Wu G
通讯作者：
Wu G