Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A central point of regulation in the Wnt/beta-catenin signalling pathway is the formation of the beta-catenin destruction complex. Axin1, an essential negative regulator of Wnt signalling, serves as a scaffold within this complex and is critical for rapid turnover of beta-catenin. To examine the mechanism by which Wnt signalling disables the destruction complex, we used an immunoprecipitation-coupled proteomics approach to identify novel endogenous binding partners of Axin1. We found mitogen-activated protein kinase kinase kinase 1 (MAP3K1) as an Axin1 interactor in Ls174T colorectal cancer (CRC) cells. Importantly, confirmation of this interaction in HEK293T cells indicated that the Axin1-MAP3K1 interaction is induced and modulated by Wnt stimulation. siRNA depletion of MAP3K1 specifically abrogated TCF/LEF-driven transcription and Wnt3A-driven endogenous gene expression in both HEK293T as well as DLD-1 CRC. Expression of ubiquitin ligase mutants of MAP3K1 abrogated TCF/LEF transcription, whereas kinase mutants had no effect in TCF-driven activity, highlighting the essential role of the MAP3K1 E3 ubiquitin ligase activity in regulation of the Wnt/beta-catenin pathway. These results suggest that MAP3K1, previously reported as an Axin1 inter-actor in c-Jun NH(2)-terminal kinase pathway, is also involved in the canonical Wnt signalling pathway and positively regulates expression of Wnt target genes.
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PMID:MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway. 2012 90

(1) Background: Epithelial-mesenchymal transition (EMT) and cancer cell stemness maintenance (SM) are important factors for cancer metastasis. Although hypoxia has been considered as a possible factor for EMT induction and promotion of SM, studies in this area, apart from hypoxia-inducible factor (HIF) pathways and severe hypoxia, are scant. This study aimed to evaluate the effects of different oxygen levels on EMT induction and SM and elucidate the signaling pathways involved in colorectal cancer cells. (2) Methods: Cell morphological analysis, migration assay, immunofluorescence staining of cytoskeleton and Western blotting were performed on human colorectal cancer cells HT-29, DLD-1, and SW-480 cultured at 1%, 10%, and normal (21%) O2 levels. The role played by c-Jun N-terminal kinase (JNK) was evaluated through the use of the specific JNK inhibitor SP600125. (3) Results: This study evaluated 1% and 10% O2 are possible conditions for EMT induction and SM. This study also demonstrated the partial relieve of EMT induction and SM by SP600125, showing the importance of the JNK pathway in these processes. Furthermore, this study proposed a novel pathway on the regulation of Akt by JNK-c-Jun. (4) Conclusions: This study suggests 10% O2 as another possible condition for EMT induction, and SM and JNK pathways play important roles in these processes through multiple factors. Inhibition of JNK could be explored as treatment for inhibiting metastasis in colorectal cancer cells.
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PMID:JNK Pathway Mediates Low Oxygen Level Induced Epithelial-Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer Cells. 3196 5


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