Epithelial-Mesenchymal Transition Induced by Growth Suppressor p12CDK2-AP1 Promotes Tumor Cell Local Invasion but Suppresses Distant Colony Growth
| العنوان: | Epithelial-Mesenchymal Transition Induced by Growth Suppressor p12CDK2-AP1 Promotes Tumor Cell Local Invasion but Suppresses Distant Colony Growth |
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| المؤلفون: | Takanori Tsuji, Akira Sasaki, Guo-fu Hu, Soichiro Ibaragi, Kaori Shima, Miaofen G. Hu, Miki Katsurano |
| المصدر: | Cancer Research. 68:10377-10386 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Keratinocytes, Cancer Research, Cell type, Pathology, medicine.medical_specialty, Lung Neoplasms, Mice, Nude, Transfection, Article, Metastasis, Mesoderm, Mice, Transforming Growth Factor beta, Cricetinae, medicine, Animals, Humans, Neoplasm Invasiveness, Epithelial–mesenchymal transition, Neoplasm Metastasis, Mouth neoplasm, Mice, Inbred BALB C, biology, Tumor Suppressor Proteins, Intravasation, Epithelial Cells, Transforming growth factor beta, Cadherins, medicine.disease, Extravasation, Oncology, embryonic structures, biology.protein, Cancer research, Mouth Neoplasms, Protein Kinases |
| الوصف: | Epithelial-mesenchymal transition (EMT) has been considered essential for metastasis, a multistep process including local invasion, intravasation, extravasation, and proliferation at distant sites. However, controversy remains as to whether EMT truly happens and how important it is to metastasis. We studied the involvement of EMT in individual steps of metastasis and found that p12CDK2-AP1, a down-stream effector of transforming growth factor β, induced EMT of hamster cheek pouch carcinoma-1 cells by promoting the expression of Twist2. EMT cells have an increased invasive but decreased metastatic phenotype. When s.c. inoculated, both EMT and non-EMT cells established primary tumors, but only EMT cells invaded into the adjacent tissues and blood vessels; however, neither cells formed lung metastases. When i.v. inoculated, only non-EMT cells established lung metastases. Moreover, s.c. inoculation of a mixture of the two cell types resulted in intravasation of both cell types and formation of lung metastasis from non-EMT cells. Our results allowed us to propose a novel model for the role of EMT in cancer metastasis. We showed that EMT and non-EMT cells cooperate to complete the spontaneous metastasis process. We thus hypothesize that EMT cells are responsible for degrading the surrounding matrix to lead the way of invasion and intravasation. Non-EMT cells then enter the blood stream and reestablish colonies in the secondary sites. [Cancer Res 2008;68(24):10377–86] |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0cd1e1f68e9715109843238d97bf3127Test https://doi.org/10.1158/0008-5472.can-08-1444Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0cd1e1f68e9715109843238d97bf3127 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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