ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer
| Autor: | Yanmei Zou, Xin Lu, Hua Xiong, Yilu Zhou, Dian Liu, Yihua Wang, Xianglin Yuan, Charlotte Hill, Ayse Ertay, Hong Qiu, Juanjuan Li, Rob M. Ewing |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cancer Research Epithelial-Mesenchymal Transition Colorectal cancer Immunology Mice Nude Article Metastasis Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation In vivo Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness Cell migration Epithelial–mesenchymal transition Neoplasm Metastasis lcsh:QH573-671 Adaptor Proteins Signal Transducing Neoplasm Staging Cancer Tissue microarray business.industry lcsh:Cytology Signal transducing adaptor protein Cell Biology Middle Aged HCT116 Cells medicine.disease digestive system diseases 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Cancer research Heterografts Female Apoptosis Regulatory Proteins Colorectal Neoplasms business |
| Zdroj: | Cell Death and Disease, Vol 11, Iss 4, Pp 1-13 (2020) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin- dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients. |
| Databáze: | OpenAIRE |
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