Dataset Information

Quantitative proteomic Analysis Reveals up-regulation of caveolin-1 inFOXP3-overexpressed human gastric cancer cells

ABSTRACT: Forkhead box protein 3 (FOXP3) is associated with tumor progression and prognosis in various types of tumor cells. We have recently reported that FOXP3 inhibited proliferation of gastric cancer (GC) cells through activating the apoptotic signaling pathway. In this study, we found that over-expression of FOXP3 inhibited GC cell migration, invasion and proliferation. To further investigate the down-stream proteins regulated by FOXP3, the label-free quantitative proteomic approach was employed to analyze the gastric cells stably transfected with FOXP3-containing lentivirus or empty vector. A total of 3,978 proteins were identified and quantified, including 186 significantly changed proteins. Caveolin-1 (CAV1) was one of those changed proteins up-regulated in FOXP3-overexpressed gastric cells, moreover, it is one of the node proteins in the protein-protein interaction network and the key protein involved in focal adhesion pathway by bioinformatics analysis. As the main constituent of caveolae, caveolin-1 interacts directly with several signaling molecules and acts as a tumor suppressor in numerous carcinomas. Further biological experiments confirmed that FOXP3 directly binded to the promoter regions of CAV1 to positively regulated CAV1 transcription in GC cells. In summary, our study suggested that FOXP3 plays a tumor-suppressing role in GC via positively regulating CAV1 through transcriptional activation, and this FOXP3-CAV1 transcriptional regulation ais may play an important role in inhibiting invasion and metastasis of GC cells.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jing Gao

PROVIDER: PXD054940 | iProX | Fri Aug 16 00:00:00 BST 2024

REPOSITORIES: iProX

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Quantitative proteomic Analysis Reveals up-regulation of caveolin-1 in FOXP3-overexpressed human gastric cancer cells.

Pan Duyi D Gao Jing J Zeng Xiaoqing X Ma Guifen G Li Na N Huang Xiaoquan X Du Xuanling X Miao Qing Q Lian Jingjing J Xu Lili L Zhou Hu H Chen Shiyao S

Scientific reports 20171031 1

Forkhead box protein 3 (FOXP3) is implicated in tumor progression and prognosis in various types of tumor cells. We have recently reported that FOXP3 inhibited proliferation of gastric cancer (GC) cells through activating the apoptotic signaling pathway. In this study, we found that over-expression of FOXP3 inhibited GC cell migration, invasion and proliferation. Then, the label-free quantitative proteomic approach was employed to further investigating the down-stream proteins regulated by FOXP3 ...[more]

PMID: 29089565

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Project description:Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, has been reported to be overexpressed in several types of solid tumors and contributes to epigenetic silencing of tumor suppressor. However, its clinical significance and the molecular mechanisms underlying its regulation in gastric cancer (GC) remain largely unknown. Here, we showed that CUL4B was elevated in GC tissues and its overexpression was positively correlated with poor prognosis and lymph node metastasis. CUL4B knockdown in GC cells decreased proliferation, mesenchymal transition and invasion in vitro, as well as tumor growth and metastasis in nude mice, and CUL4B overexpression induced the opposite results. Further studies showed that miR-101 could inhibit CUL4B expression by directly targeting its 3’-UTR and they were inversely correlated in clinical GC specimens. Notably, a positive relationship between CUL4B and HER2 was found in GC clinical specimens, GC cells and GC xenograft tumors. Through bioinformatics analysis of miRNA-seq data and target prediction, we nominated miR-125a as a direct target of CUL4B. ChIP assays demonstrated that CUL4B directly repressed miR-125a expression by physically binding to its promoter. In addition, we confirmed miR-125a is the target of HER2. Consequently, we demonstrated that CUL4B can up-regulate HER2 expression through repressing miR-125a. Most importantly, silencing of HER2 by Herceptin or siRNA partially reversed CUL4B-induced epithelial-to-mesenchymal transition (EMT), cell invasion and metastasis in vitro and in vivo. These findings define a CUL4B-miR-125a-HER2 regulatory mechanism shed light on CUL4B oncogenic mechanisms and reveals promising therapeutic targets for progressive GC. CUL4B proteins are frequently upregulated in human cancer, yet little is known about the underlying molecular mechanisms of CUL4B induced gastric cancer(GC) carcigenesis.Here, we uncover the critical role of CUL4B in gastric cancer growth and metastasis through the regulation of HER2 expression.CUL4B contributes to GC invasion and metastasis by transcriptional repression of HER2 targeting miR-125a, which provide a new insight into how CUL4B regulates GC progression and metastasis.

Dataset Information

Quantitative proteomic Analysis Reveals up-regulation of caveolin-1 inFOXP3-overexpressed human gastric cancer cells

Publications

Quantitative proteomic Analysis Reveals up-regulation of caveolin-1 in FOXP3-overexpressed human gastric cancer cells.

Similar Datasets

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