The LIM protein Ajuba promotes a metastatic phenotype in colon cancer cells
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ABSTRACT:
PROVIDER: PRJNA613026 | ENA |
REPOSITORIES: ENA
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Project description:RNA-seq of Colon cancer cell line Sw480 with Ajuba OE and KD.Colon cancer, along with its potential for recurrence and metastasis is a major health problem. Understanding the proteins and pathways that regulate cell growth and metastasis may provide new targets for patient care. Ajuba is a LIM domain protein often found overexpressed in cancers, however the exact function role of Ajuba in colon cancer is not known. Our data demonstrates that Ajuba is highly expressed in colon cancer cell lines and tumour tissue compared to adjacent non-tumour tissue. Using publicly available data from The Cancer Genome Atlas, we correlated poor colon cancer patient survival with high Ajuba expression. To investigate the function of Ajuba in colon cancer metastasis we transduced cells with lentiviral constructs to knock down and overexpress Ajuba protein and performed an RNA-seq transcriptomic analysis on each modified line. Analysing the pathways enriched in the differentially expressed genes, we found Ajuba to be involved in cell proliferation, migration and differentiation. We confirmed our findings in biological assays, cells depleted of Ajuba were less proliferative, more sensitive to irradiation, migrated less and were less efficient in colony formation. Our data indicates that increased Ajuba expression observed in colon cancer supports proliferation, epithelial-to-mesenchymal transition and metastasis.
2020-07-25 | GSE147111 | GEO
Project description:Protein ubiquitination is essential for multiple physiological processes through regulating the stability or function of target proteins and has been found to play critical roles in human cancers. However, the protein ubiquitination profile of human metastatic colon adenocarcinoma tissue has not been elucidated yet. In this study, a proprietary ubiquitin branch (K-ε-GG) antibody-based label-free quantitative proteomics and bioinformatics were performed to identify the global protein ubiquitination profile between human primary (Colon) and metastatic colon adenocarcinoma (Meta) tissues.
2020-07-27 | PXD020597 | iProX
Project description:Comparison of gene expression between poorly metastatic HCT116 colon cancer cell line and the in-vivo derived metastatic E1 cell line, which has EMT (epithelial to mesenchymal transition) features.
2011-03-01 | GSE13759 | GEO
Project description:Comparison of gene expression between poorly metastatic HCT116 colon cancer cell line and the in-vivo derived metastatic E1 cell line, which has EMT (epithelial to mesenchymal transition) features. Each cell line has triplicate chips.
2011-03-01 | E-GEOD-13759 | biostudies-arrayexpress
Project description:How cells in primary tumors initially become pro-metastatic is not understood. A previous genome-wide RNAi screen uncovered colon cancer metastatic suppressor and WNT promoting functions of TMED3, a member of the p24 ER-to-Golgi protein secretion family. Repression of WNT signaling upon knock-down (kd) of TMED3 might thus be sufficient to drive metastases. However, searching for transcriptional influences on other family members here we find that TMED3 kd leads to enhanced TMED9, that TMED9 acts downstream of TMED3 and that TMED9 kd compromises metastasis. Importantly, TMED9 pro-metastatic function is linked to but distinct from the repression of TMED3-WNT-TCF signaling. Functional rescue of the migratory deficiency of TMED9 kd cells identifies TGFa as a mediator of TMED9 pro-metastatic activity. Moreover, TMED9 kd compromises the membrane localization, and thus function, of TGFa. Analyses in three colon cancer cell types highlight a TMED9-dependent gene set that includes CNIH4, a member of the CORNICHON family of TGFa exporters. Our data indicate that TGFA and CNIH4, which display predictive value for disease-free survival, promote colon cancer cell metastatic behavior and suggest that TMED9 pro-metastatic function involves the modulation of the secretion of TGFa ligand. Finally, TMED9/TMED3 antagonism impacts WNT-TCF and GLI signaling, where TMED9 primacy over TMED3 leads to the establishment of a positive feedback loop together with CNIH4, TGFa and GLI1 that enhances metastases. We suggest that primary colon cancer cells can transition between two states characterized by secretion-transcription regulatory loops gated by TMED3 and TMED9 that modulate their metastatic proclivities.
2019-07-01 | GSE125282 | GEO
Project description:Here, we report the genomic-scale characterization of metastatic colon cancer transcriptome. Fresh-frozen samples was used to asses differences between normal colon, primary colon tumor an liver metastasis.
2018-09-22 | GSE89393 | GEO
Project description:Four and a half LIM domains protein 2 (FHL2) is a co-regulator of gene transcription relevant for many signalling pathways and physiological processes. In this work, the role of FHL2 in cell differentiation has been investigated during in vitro mineralization using a Sparus aurata pre-osteoblast cell line (VSa16, [1]). A global microarray analysis was then performed to characterize the molecular pathways affected by FHL2 overexpression. [1] Pombinho, A.R., LaizM-CM-), V., Molha, D.M., Marques, S.M.P. and Cancela, M.L. (2004). Development of two bone-derived cell lines from the marine teleost Sparus aurata; evidence for extracellular matrix mineralization and cell-type specific expression of matrix Gla protein and osteocalcin. Cell Tissue Res. 315, 393-406. Sparus aurata oligo-DNA microarray (GPL6467) was used to compare gene expression profiles between Control (WT) and FHL2-transfected (F2) VSa16 cell lines. Gene expression profiles of both WT and F2 cells were assessed either at T0 (initial confluent cultures) or T4 (4 weeks of cell confluency). Four (4) pools of cells were taken from both WT and F2 groups at each time point and stored in RNA later at -20M-BM-0C until RNA extraction.
2013-01-03 | E-GEOD-32501 | biostudies-arrayexpress
Project description:Four and a half LIM domains protein 2 (FHL2) is a co-regulator of gene transcription relevant for many signalling pathways and physiological processes. In this work, the role of FHL2 in cell differentiation has been investigated during in vitro mineralization using a Sparus aurata pre-osteoblast cell line (VSa16, [1]). A global microarray analysis was then performed to characterize the molecular pathways affected by FHL2 overexpression. [1] Pombinho, A.R., Laizé, V., Molha, D.M., Marques, S.M.P. and Cancela, M.L. (2004). Development of two bone-derived cell lines from the marine teleost Sparus aurata; evidence for extracellular matrix mineralization and cell-type specific expression of matrix Gla protein and osteocalcin. Cell Tissue Res. 315, 393-406.
2013-01-03 | GSE32501 | GEO
Project description:Bacillus sp. TYF-LIM-B05 strain:TYF-LIM-R05 Genome sequencing and assembly
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Project description:Characterization of the intra-tumoral heterogeneity between two iso-clonal human colon cancer sublines HCT116 and HCT116b on their ability to undergo metastatic colonization and survive under growth factor deprivation stress (GFDS). Microarray analysis revealed an upregulation of survival and metastatic genes in the highly metastatic HCT116 primary colon tumor cells compared to the poorly metastatic HCT116b primary colon tumor cells.
2013-02-20 | GSE44381 | GEO