ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer
Open Access
- 8 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (4), 1-13
- https://doi.org/10.1038/s41419-020-2415-2
Abstract
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.Keywords
This publication has 58 references indexed in Scilit:
- Expression pattern of the apoptosis-stimulating protein of p53 family in p53+ human breast cancer cell linesCancer Cell International, 2013
- Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factorsClinical Epidemiology, 2012
- Autophagic activity dictates the cellular response to oncogenic RASProceedings of the National Academy of Sciences of the United States of America, 2012
- A Comprehensive Survey of Ras Mutations in CancerCancer Research, 2012
- Epithelial–Mesenchymal Transition Induced by TNF-α Requires NF-κB–Mediated Transcriptional Upregulation of Twist1Cancer Research, 2012
- Tumor Metastasis: Molecular Insights and Evolving ParadigmsCell, 2011
- SUMO-modified nuclear cyclin D1 bypasses Ras-induced senescenceCell Death & Differentiation, 2010
- TNF-α/NF-κB/Snail pathway in cancer cell migration and invasionBritish Journal of Cancer, 2010
- Constitutive NF-κB Activation in Colorectal Carcinoma Plays a Key Role in Angiogenesis, Promoting Tumor GrowthClinical Cancer Research, 2009
- Formation of Cysts by Alveolar Type II Cells in Three-dimensional Culture Reveals a Novel Mechanism for Epithelial MorphogenesisMolecular Biology of the Cell, 2007