Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin
Open Access
- 4 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 12 (2), 1-15
- https://doi.org/10.1038/s41419-021-03424-1
Abstract
The homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.Keywords
This publication has 60 references indexed in Scilit:
- Long-range transcriptional regulation by the p110 CUX1 homeodomain protein on theENCODE arrayBMC Genomics, 2013
- Optimizing chemotherapy and radiotherapy for anaplastic gliomaNature Reviews Clinical Oncology, 2010
- The roles of CUX1 homeodomain proteins in the establishment of a transcriptional program required for cell migration and invasionCell Adhesion & Migration, 2010
- Cux1 and Cux2 Regulate Dendritic Branching, Spine Morphology, and Synapses of the Upper Layer Neurons of the CortexNeuron, 2010
- p110 CUX1 Homeodomain Protein Stimulates Cell Migration and Invasion in Part through a Regulatory Cascade Culminating in the Repression of E-cadherin and OccludinOnline Journal of Public Health Informatics, 2009
- Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic TypesCancer Research, 2009
- PTEN/PI3K/Akt Pathway Regulates the Side Population Phenotype and ABCG2 Activity in Glioma Tumor Stem-like CellsCell Stem Cell, 2009
- WNT5A--target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancerCarcinogenesis: Integrative Cancer Research, 2007
- The N-terminal Region of the CCAAT Displacement Protein (CDP)/Cux Transcription Factor Functions as an Autoinhibitory Domain that Modulates DNA BindingOnline Journal of Public Health Informatics, 2004
- Coexpression of Cux‐1 and notch signaling pathway components during kidney developmentDevelopmental Dynamics, 2004