Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Bodmer, N; Uth, K; Mehmeti, R; Demir, CS; Stroka, D; Ghaffari-Tabrizi-Wizsy, N; Lugli, A; de, Wever, O; Zlobec, I; Tschan, MP.
CDX2 loss in colorectal cancer cells is associated with invasive properties and tumor budding.
Sci Rep. 2025; 15(1): 24113
Doi: 10.1038/s41598-025-07278-x
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- Co-authors Med Uni Graz
- Ghaffari Tabrizi-Wizsy Nassim
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- Abstract:
- In colorectal cancer (CRC), tumor buds (TB) are observed histologically as single tumor cell or small tumor cell clusters located mainly at the advancing tumor edge. TB are a marker of poor prognosis and correlate with metastatic disease in CRC patients. They often lack expression of CDX2 and overexpress markers involved in epithelial-mesenchymal transition (EMT). We evaluated the function of CDX2 in CRC proliferation and migration using CRISPR/Cas9 technology and demonstrated a possible link to tumor dissociation and tumor budding. Knocking out CDX2 in CRC cell lines significantly increased migration. Importantly, the observed phenotypes could be rescued by re-expressing CDX2 and by specific CRISPR synergistic activation mediator (SAM) of endogenous CDX2 in CDX2 low expressing CRC cell lines. Multiplex immunofluorescence (mIF) analysis of primary tumor regions compared to TB in a CDX2-positive CRC patient sample as well as patient derived xenografts (PDX) revealed significantly lower CDX2 expression and correlating E-cadherin levels in TB compared to primary tumor regions, in both models. Accordingly, increased invasiveness of CRC CDX2 knockout cells was seen in ex ovo xenografts. Taken together, our results provide further insight into the function of CDX2 in preventing CRC cell migration, tumor budding and tumor aggressiveness.
- Find related publications in this database (using NLM MeSH Indexing)
- CDX2 Transcription Factor - genetics, metabolism
- Colorectal Neoplasms - pathology, genetics, metabolism
- Humans - administration & dosage
- Animals - administration & dosage
- Cell Movement - genetics
- Cell Line, Tumor - administration & dosage
- Neoplasm Invasiveness - administration & dosage
- Mice - administration & dosage
- Cell Proliferation - administration & dosage
- Epithelial-Mesenchymal Transition - genetics
- Cadherins - metabolism
- Gene Expression Regulation, Neoplastic - administration & dosage
- CRISPR-Cas Systems - administration & dosage
- Find related publications in this database (Keywords)
- Colorectal cancer
- CDX2
- Tumor budding
- Cell migration
- EMT