PDLIM1 Stabilizes the E-Cadherin/β-Catenin Complex to Prevent Epithelial–Mesenchymal Transition and Metastatic Potential of Colorectal Cancer Cells
| العنوان: | PDLIM1 Stabilizes the E-Cadherin/β-Catenin Complex to Prevent Epithelial–Mesenchymal Transition and Metastatic Potential of Colorectal Cancer Cells |
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| المؤلفون: | Edouard C. Nice, Kefei Yuan, Canhua Huang, Yan Chen, Zhao Huang, Hai-Ning Chen, Na Xie, Min Wu, Qianhui Dou, Kui Wang, Zong-Guang Zhou |
| المصدر: | Cancer Research. 76:1122-1134 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Beta-catenin, Colorectal cancer, Mouse model of colorectal and intestinal cancer, Biology, Metastasis, Mice, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Cell Line, Tumor, Internal medicine, medicine, Animals, Humans, Neoplasm Invasiveness, Epithelial–mesenchymal transition, Promoter Regions, Genetic, beta Catenin, Mice, Inbred BALB C, Protein Stability, Cadherin, Liver Neoplasms, DNA Methylation, LIM Domain Proteins, Cadherins, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Catenin complex, Colorectal Neoplasms, Protein Binding, Transcription Factors |
| الوصف: | Metastasis is a major cause of death in patients with colorectal cancer, and increasing evidence supports the contribution of the epithelial–mesenchymal transition (EMT) to cancer progression. The dissociation of the E-cadherin/β-catenin adhesion complex represents a key step in EMT and promotes cancer invasion and metastasis, but the upstream signaling pathways regulating this interaction are poorly understood. Here, we show that PDLIM1, a member of the PDZ and LIM protein family, was downregulated in highly metastatic colorectal cancer cells and liver metastases from colorectal cancer patients. We found that loss of PDLIM1 promoted the expression of EMT markers and increased the invasive and migratory properties of multiple colorectal cancer cell lines. Furthermore, PDLIM1 knockdown increased colon-derived liver metastasis in an orthotopic colorectal cancer model and promoted distant metastatic colonization in an experimental lung metastasis model. Mechanistic investigations revealed that PDLIM1 interacted with and stabilized the E-cadherin/β-catenin complex, thereby inhibiting the transcriptional activity of β-catenin and preventing EMT. Accordingly, PDLIM1 overexpression attenuated EMT of colorectal cancer cells. Moreover, the downregulation of PDLIM1 in colorectal cancer samples correlated with reduced E-cadherin and membrane β-catenin levels, and was associated with shorter overall survival. In conclusion, our study demonstrates that PDLIM1 suppresses EMT and metastatic potential of colorectal cancer cells by stabilizing β-catenin at cell–cell junctions, and its loss in metastatic tissues may represent a potential prognostic marker of aggressive disease. Cancer Res; 76(5); 1122–34. ©2015 AACR. |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24740f67ab822a5f5cb2113b1f6ac939Test https://doi.org/10.1158/0008-5472.can-15-1962Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....24740f67ab822a5f5cb2113b1f6ac939 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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