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Updated: Mar 15, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
CEACAM1 controls the EMT switch in murine mammary carcinoma in vitro and in vivo
Florian Wegwitz1,2, Eva Lenfert2, Daniela Gerstel3
1Clinic for General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Georg-August-University of Göttingen, D-37077 Göttingen, Germany.
Abstract:
We analyzed the molecular basis for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-controlled inhibition of epithelial-mesenchymal transition (EMT) in a mouse model for mammary adenocarcinoma (WAP-T mice). We demonstrate that silencing of CEACAM1 in WAP-T tumor-derived G-2 cells induces epithelial-mesenchymal plasticity (EMP), as evidenced by typical changes of gene expression, morphology and increased invasion. In contrast, reintroduction of CEACAM1 into G-2 cells reversed up-regulation of genes imposing mesenchymal transition, as well as cellular invasion. We identified the Wnt-pathway as target for CEACAM1-mediated repression of EMT. Importantly, β-catenin phosphorylation status and transcriptional activity strongly depend on CEACAM1 expression: CEACAM1high G-2 cells displayed enhanced phosphorylation of β-catenin at S33/S37/T41 and decreased phosphorylation at Y86, thereby inhibiting canonical Wnt/β-catenin signaling. We identified Src-homology 2 domain-containing phosphatase 2 (SHP-2) as a critical binding partner of CEACAM1 that could modulate β-catenin Y86 phosphorylation. Hence, CEACAM1 serves as a scaffold that controls membrane proximal β-catenin signaling. In vivo, mammary tumors of WAP-T/CEACAM1null mice displayed increased nuclear translocation of β-catenin and a dramatically enhanced metastasis rate compared to WAP-T mice. Hence, CEACAM1 controls EMT in vitro and in vivo by site-specific regulation of β-catenin phosphorylation. Survival analyses of human mammary carcinoma patients corroborated these data, indicating that CEACAM1 is a prognostic marker for breast cancer survival.
Insights
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) inhibits epithelial-mesenchymal transition (EMT) by regulating beta-catenin phosphorylation. CEACAM1 acts as a prognostic marker for breast cancer survival.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Epithelial-mesenchymal transition (EMT) is crucial for cancer progression and metastasis.
- CEACAM1 is a cell adhesion molecule with known roles in cell-cell interactions.
- The precise molecular mechanisms by which CEACAM1 influences EMT are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying CEACAM1-mediated inhibition of EMT in mammary adenocarcinoma.
- To investigate the role of CEACAM1 in regulating beta-catenin signaling and Wnt pathway activity.
- To evaluate CEACAM1 as a prognostic marker in human breast cancer.
Main Methods:
- Analysis of CEACAM1 function in a mouse model of mammary adenocarcinoma (WAP-T mice).
- In vitro studies using CEACAM1-silenced and re-expressing tumor cells (G-2 cells).
- Assessment of gene expression, cell morphology, invasion, beta-catenin phosphorylation, and protein interactions (SHP-2).
- In vivo validation in WAP-T/CEACAM1null mice and survival analysis of human breast cancer patient data.
Main Results:
- Silencing CEACAM1 in G-2 cells induced EMT, characterized by altered gene expression, morphology, and increased invasion.
- Reintroduction of CEACAM1 reversed EMT phenotypes and reduced cellular invasion.
- CEACAM1 inhibited canonical Wnt/beta-catenin signaling by promoting beta-catenin phosphorylation at S33/S37/T41 and reducing it at Y86.
- SHP-2 was identified as a binding partner of CEACAM1, modulating beta-catenin Y86 phosphorylation.
- Mammary tumors in CEACAM1-deficient mice showed increased beta-catenin nuclear translocation and enhanced metastasis.
- Human breast cancer patient data confirmed CEACAM1 as a prognostic marker for survival.
Conclusions:
- CEACAM1 controls EMT in vitro and in vivo through site-specific regulation of beta-catenin phosphorylation.
- CEACAM1 functions as a scaffold protein regulating membrane-proximal beta-catenin signaling.
- CEACAM1 is a valuable prognostic biomarker for breast cancer survival.
