The control of tissue architecture over nuclear organization is crucial for epithelial cell fate
Author:
Chandramouly Gurushankar1, Abad Patricia C.1, Knowles David W.2, Lelièvre Sophie A.1
Affiliation:
1. Department of Basic Medical Sciences and Cancer Center, Purdue University, 625 Harrison Street, West Lafayette, IN 47907-2026, USA 2. Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
Abstract
The remodeling of nuclear organization during differentiation and the dramatic alteration of nuclear organization associated with cancer development are well documented. However, the importance of tissue architecture in the control of nuclear organization remains to be determined. Differentiation of mammary epithelial cells into functional tissue structures, in three-dimensional culture, is characterized by a specific tissue architecture (i.e. a basoapical polarity axis), cell cycle exit and maintenance of cell survival. Here we show that induction of partial differentiation (i.e. basal polarity only, cell cycle exit and cell survival) by epigenetic mechanisms in malignant breast cells is sufficient to restore features of differentiation-specific nuclear organization, including perinucleolar heterochromatin, large splicing factor speckles, and distinct nuclear mitotic apparatus protein (NuMA) foci. Upon alteration of nuclear organization using an antibody against NuMA, differentiated non-neoplastic cells undergo apoptosis, whereas partially differentiated malignant cells enter the cell cycle. Non-neoplastic cells cultured under conditions that prevent the establishment of apical polarity also enter the cell cycle upon NuMA antibody treatment. These findings demonstrate that the differentiation status rather than the non-neoplastic or neoplastic origin of cells controls nuclear organization and suggest a link between nuclear organization and epigenetic mechanisms dictated by tissue architecture for the control of cell behavior.
Publisher
The Company of Biologists
Reference65 articles.
1. Abad, P. C., Mian, I. S., Plachot, C., Nelpurackal, A., Bator-Kelly, C. and Lelièvre, S. A. (2004). The C terminus of the nuclear protein NuMA: phylogenetic distribution and structure. Protein Sci.13, 2573-2577. 2. Abad, P. C., Lewis, J., Mian, I. S., Knowles, D. W., Sturgis, J., Badve, S., Xie, J. and Lelièvre, S. A. (2007). NuMA influences higher order chromatin organization in human mammary epithelium. Mol. Biol. Cell18, 348-361. 3. Aijaz, S., Balda, M. S. and Matter, K. (2006). Tight junctions: molecular architecture and function. Int. Rev. Cytol.248, 261-298. 4. Andre, C., Guillemin, M. C., Zhu, J., Koken, M. H., Quignon, F., Herve, L., Chelbi-Alix, M. K., Dhumeaux, D., Wang, Z. Y., Degos, L. et al. (1996). The PML and PML/RARalpha domains: from autoimmunity to molecular oncology and from retinoic acid to arsenic. Exp. Cell Res.229, 253-260. 5. Ang, S. L. and Constam, D. B. (2004). A gene network establishing polarity in the early mouse embryo. Semin. Cell Dev. Biol.15, 555-561.
Cited by
61 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|