ZNF37A promotes tumor metastasis through transcriptional control of THSD4/TGF-β axis in colorectal cancer
| العنوان: | ZNF37A promotes tumor metastasis through transcriptional control of THSD4/TGF-β axis in colorectal cancer |
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| المؤلفون: | Yuquan Wei, Zhao Huang, Zong-Guang Zhou, Jingwen Jiang, Jiayang Liu, Yan Chen, Hai-Ning Chen, Canhua Huang, Qin Ye, Maochao Luo, Ke Xie, Siyuan Qin, Na Xie, Zhe Zhang |
| المصدر: | Oncogene. 40:3394-3407 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cancer Research, Stromal cell, Colorectal cancer, Kruppel-Like Transcription Factors, Mice, Nude, Biology, Metastasis, Mice, 03 medical and health sciences, 0302 clinical medicine, Cancer-Associated Fibroblasts, Downregulation and upregulation, Cell Movement, Transforming Growth Factor beta, Cell Line, Tumor, Tumor Microenvironment, Genetics, Transcriptional regulation, medicine, Animals, Humans, Neoplasm Metastasis, Fibroblast, neoplasms, Molecular Biology, Mice, Inbred BALB C, Tumor microenvironment, Serine Endopeptidases, Membrane Proteins, medicine.disease, digestive system diseases, Survival Rate, ADAM Proteins, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Disease Progression, Cancer research, Heterografts, Colorectal Neoplasms, Transforming growth factor |
| الوصف: | Poorly differentiated colorectal cancer (CRC) is characterized by aggressive invasion and stromal fibroblast activation, which results in rapid progression and poor therapeutic consequences. However, the regulatory mechanism involved remains unclear. Here, we showed that ZNF37A, a member of KRAB-ZFP family, was upregulated in poorly differentiated CRCs and associated with tumor metastasis. ZNF37A enhanced the metastatic potential of multiple CRC cell lines and promoted distant metastasis in an orthotopic CRC model. Further investigation attributed the ZNF37A-exacerbated metastasis to increased extracellular TGF-β and the consequent activation of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME). Mechanistically, ZNF37A formed a complex with KAP1 and bound to the promoter of THSD4, a TME modulator, to suppress its transcription, which is required for ZNF37A-mediated TGF-β activation and CRC metastasis. Collectively, our study indicates that ZNF37A promotes TGF-β signaling in CRC cells and activates CAFs by transcriptionally repressing THSD4 to drive CRC metastasis, implicating ZNF37A as a potential biomarker for CRC differentiation and progression. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9bf31f8f1a0176f6bd72bed75663d3c3Test https://doi.org/10.1038/s41388-021-01713-9Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....9bf31f8f1a0176f6bd72bed75663d3c3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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