BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins
| العنوان: | BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins |
|---|---|
| المؤلفون: | Ying Huang, Meng Jiang, Peter S. Dennis, Runsheng Chen, Keith Alder, Yu Xin, Ruben D. Carrasco, Ruiyang Liu, Helen Tanton, Amitabh Srivastava, Mengyun Zhang, Massimo Loda, Tomasz Sewastianik, Yue Kang, Jiao Wang, Ming Liu, Zhongqiu Wang |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell biology, Molecular biology, Colorectal cancer, Science, General Physics and Astronomy, Cell Communication, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, BCL9, Cell Line, Tumor, medicine, Animals, Humans, lcsh:Science, Wnt Signaling Pathway, beta Catenin, Cancer, Tumor microenvironment, Multidisciplinary, Oncogene, Wnt signaling pathway, Paraspeckle, General Chemistry, medicine.disease, 3. Good health, Gene Expression Regulation, Neoplastic, Wnt Proteins, 030104 developmental biology, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, lcsh:Q, Calcium, Colorectal Neoplasms, Protein Binding, Transcription Factors |
| الوصف: | Colorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention. BCL9 is an activator of oncogenic Wnt/β-catenin. Here, the authors show a β-catenin independent function of BCL9 in a subtype of colorectal cancers, where it interacts with paraspeckle proteins to enhance the mRNA stability of calcium signalling and neural associated genes to promote communication with tumour cells and its microenvironment. |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afc12fda6f5787a87aac976d30cc8cc0 https://doi.org/10.1038/s41467-019-13842-7 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....afc12fda6f5787a87aac976d30cc8cc0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
|---|