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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ishikawa, F. Ushida, K. Mori, K. Shibanuma, M. |
| Description | Country affiliation: Japan Author Affiliation: Ishikawa F ( Division of Cancer Cell Biology, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo 142-8555, Japan.); Ushida K ( Division of Cancer Cell Biology, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo 142-8555, Japan.); Mori K ( Division of Cancer Cell Biology, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo 142-8555, Japan.); Shibanuma M ( Division of Cancer Cell Biology, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo 142-8555, Japan.) |
| Abstract | Anchorage dependence of cellular growth and survival prevents inappropriate cell growth or survival in ectopic environments, and serves as a potential barrier to metastasis of cancer cells. Therefore, obtaining a better understanding of anchorage-dependent responses in normal cells is the first step to understand and impede anchorage independence of growth and survival in cancer cells and finally to eradicate cancer cells during metastasis. Anoikis, a type of apoptosis specifically induced by lack of appropriate cell-extracellular matrix adhesion, has been established as the dominant response of normal epithelial cells to anchorage loss. For example, under detached conditions, the untransformed mammary epithelial cell (MEC) line MCF-10 A, which exhibits myoepithelial characteristics, underwent anoikis dependent on classical ERK signaling. On the other hand, recent studies have revealed a variety of phenotypes resulting in cell death modalities distinct from anoikis, such as autophagy, necrosis, and cornification, in detached epithelial cells. In the present study, we characterized detachment-induced cell death (DICD) in primary human MECs immortalized with hTERT ((Tert)HMECs), which are bipotent progenitor-like cells with a differentiating phenotype to luminal cells. In contrast to MCF-10 A cells, apoptosis was not observed in detached (Tert)HMECs; instead, non-apoptotic cell death marked by features of entosis, cornification, and necrosis was observed along with downregulation of focal adhesion kinase (FAK) signaling. Cell death was overcome by anchorage-independent activities of FAK but not PI3K/AKT, SRC, and MEK/ERK, suggesting critical roles of atypical FAK signaling pathways in the regulation of non-apoptotic cell death. Further analysis revealed an important role of TRAIL (tumor necrosis factor (TNF)-related apoptosis-inducing ligand) as a mediator of FAK signaling in regulation of entosis and necrosis and a role of p38 MAPK in the induction of necrosis. Overall, the present study highlighted outstanding cell subtype or differentiation stage specificity in cell death phenotypes induced upon anchorage loss in human MECs. |
| File Format | HTM / HTML |
| e-ISSN | 20414889 |
| DOI | 10.1038/cddis.2014.583 |
| Journal | Cell Death and Disease |
| Volume Number | 6 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2015-01-22 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Entosis Cell Line Research Support, Non-u.s. Gov't P38 Mitogen-activated Protein Kinases Signal Transduction Cell Survival Cytology Epithelial Cells Metabolism Focal Adhesion Kinase 1 Cell Adhesion Necrosis Discipline Cell Biology Endocytosis Mammary Glands, Human Ultrastructure Down-regulation Up-regulation Anoikis Telomerase Apoptosis Tnf-related Apoptosis-inducing Ligand |
| Content Type | Text |
| Resource Type | Article |
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