Dataset Information

Smad1 promotes colorectal cancer cell migration through Ajuba transactivation.

ABSTRACT: SMAD family member 1 (Smad1) have been involved in metastatic progression of many cancer types. However, the detailed molecular signalling pathway underlying the regulatory link between Smad1 and metastasis remains elusive. Here, we demonstrate that Smad1 promotes migration of colorectal cancer (CRC) cells by inducing Snail and Ajuba expression simultaneously, but no apparent effect on Twist1 expression. Remarkably, E-cadherin, the best known Snail/Ajuba target gene is downregulated by Smad1 expression. Further, depletion of Ajuba in HCT116 cells significantly dampens the cell migration capability induced by Smad1 overexpression, suggesting that Ajuba is required for Smad1 to induce cell migration. Moreover, clinical analysis shows a significant positive correlation between the level of Smad1 and Ajuba in CRC samples. Together, our data provides the first evidence of the regulatory network of Smad1/Snail/Ajuba axis in CRC migration, suggesting that Smad1 and Ajuba are potential new therapeutic targets and prognostic factors for CRC.

SUBMITTER: Yang D

PROVIDER: S-EPMC5746393 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Smad1 promotes colorectal cancer cell migration through Ajuba transactivation.

Yang Daming D Hou Tieying T Li Lei L Chu Yimin Y Zhou Fengli F Xu Ying Y Hou Xinyu X Song Huan H Zhu Kai K Hou Zhaoyuan Z Peng Haixia H Jia Hao H

Oncotarget 20171130 66

SMAD family member 1 (Smad1) have been involved in metastatic progression of many cancer types. However, the detailed molecular signalling pathway underlying the regulatory link between Smad1 and metastasis remains elusive. Here, we demonstrate that Smad1 promotes migration of colorectal cancer (CRC) cells by inducing Snail and Ajuba expression simultaneously, but no apparent effect on Twist1 expression. Remarkably, E-cadherin, the best known Snail/Ajuba target gene is downregulated by Smad1 exp ...[more]

PMID: 29299158

Similar Datasets

Project description:Background Colorectal cancer (CRC) is one of the most prevalent malignant tumors with high morbidity and mortality rates worldwide. ZNF274, a member of the zinc-finger-protein family of transcription factors, is critical in chromosomal remodelling and tumorigenesis. However, the role of ZNF274 in CRC and the underlying molecular mechanisms remain unclear. Methods Immunohistochemical analysis was performed to quantify the expression of ZNF274 in human CRC tissues. The Kaplan‒Meier method was used to analyse the relationship between ZNF274 expression and CRC prognosis. The correlation between ZNF274 expression and clinical features was analyzed using Cox regression analysis. Cell proliferation and migration were evaluated by CCK-8, colony formation, and Transwell assays. The limma R package was used to analyse IL-8-related differentially expressed genes in the GSE30364 dataset. The DAVID method was used to screen significantly enriched pathways. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were performed to determine the transcriptional regulation of MRPL40 by ZNF274. Results ZNF274 was overexpressed in CRC tissues and indicated poor prognosis. High ZNF274 expression was linked to larger tumor size, invasion, lymph node metastasis, and AJCC stage. Ectopic expression promoted CRC cell proliferation and migration. Mechanistically, MRPL40 was identified as the direct target gene that transactivates the expression of ZNF274. Moreover, IL-8 upregulated ZNF274 expression in a dose-dependent manner. Downregulation of either ZNF274 or MRPL40 expression abrogated the effect of IL-8 on promoting the proliferation and migration of CRC. Conclusion This study revealed an oncogenic role of ZNF274 and the mechanism by which ZNF274 participated in IL-8-induced promotion of CRC progression. These findings demonstrate that ZNF274 could be used as a prognostic factor and potential therapeutic target for CRC treatment. Graphical abstract Image 1 Highlights • IL-8 activates ZNF274 and mitochondrial gene expression• High ZNF274 expression indicates poor prognosis in CRC patients• Ectopic expression of ZNF274 promotes CRC cell proliferation and migration• ZNF274 transcriptionally activates MRPL40• ZNF274 and MRPL40 are essential for IL8-mediated CRC progression

Dataset Information

Smad1 promotes colorectal cancer cell migration through Ajuba transactivation.

Publications

Smad1 promotes colorectal cancer cell migration through Ajuba transactivation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets