Academic Journal
Mint3-mediated L1CAM expression in fibroblasts promotes cancer cell proliferation via integrin α5β1 and tumour growth
| العنوان: | Mint3-mediated L1CAM expression in fibroblasts promotes cancer cell proliferation via integrin α5β1 and tumour growth |
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| المؤلفون: | Nakaoka, H J, Tanei, Z, Hara, T, Weng, J S, Kanamori, A, Hayashi, T, Sato, H, Orimo, A, Otsuji, K, Tada, K, Morikawa, T, Sasaki, T, Fukayama, M, Seiki, M, Murakami, Y, Sakamoto, T |
| المصدر: | Oncogenesis ; volume 6, issue 5, page e334-e334 ; ISSN 2157-9024 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2017 |
| الوصف: | Fibroblasts are some of the major cells in tumour tissues that influence tumour progression and drug resistance. However, our understanding on fibroblast-mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3 (Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even during normoxia in cancer cells, macrophages and fibroblasts. Although Mint3 promotes ATP production via glycolysis by activating HIF-1 in cancer cells and macrophages, the biological role of Mint3-mediated HIF-1 activation in fibroblasts remains unclear. To address this, we examined whether Mint3 in fibroblasts contributes to tumour growth. Mint3 depletion in mouse embryonic fibroblasts (MEFs) decreased tumour growth of co-injected human breast cancer cells, MDA-MB-231 and epidermoid carcinoma A431 cells in mice. In MEFs, Mint3 also promoted cancer cell proliferation in vitro in a cell–cell contact-dependent manner. Mint3-mediated cancer cell proliferation depended on HIF-1, and further gene expression analysis revealed that the cell adhesion molecule, L1 cell adhesion molecule (L1CAM), was induced by Mint3 and HIF-1 in fibroblasts. Mint3-mediated L1CAM expression in fibroblasts stimulated the ERK signalling pathway via integrin α5β1 in cancer cells, and promoted cancer cell proliferation in vitro and tumour growth. In cancer-associated fibroblasts (CAFs), knockdown of MT1-MMP, which promotes Mint3-mediated HIF-1 activation, or Mint3 decreased L1CAM expression. As MEFs, CAFs also promoted cancer cell proliferation in vitro , and tumour growth via Mint3 and L1CAM. In human breast cancer specimens, the number of fibroblasts expressing L1CAM, Mint3 and MT1-MMP was higher in cancer regions than in adjacent benign regions. In addition, more phospho-ERK1/2-positive cancer cells existed in the peripheral region surrounded by the stroma than in the central region of solid breast cancer nest. Thus, Mint3 in fibroblasts might be a good target for cancer therapy by regulating cancer cell-stromal cell ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/oncsis.2017.27 |
| الاتاحة: | http://dx.doi.org/10.1038/oncsis.2017.27 https://www.nature.com/articles/oncsis201727.pdf https://www.nature.com/articles/oncsis201727 http://www.nature.com/doifinder/10.1038/oncsis.2017.27 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.311B7C20 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/oncsis.2017.27 |
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