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Rich66 · 06-24-2009, 04:31 PM

1: Stem Cells. 2009 Jun 18. [Epub ahead of print]: Snail and Slug mediate radio- and chemo-resistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells.

Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY, Bapat SA.
National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind, Pune 411 007, INDIA.
The transcriptional repressors Snail and Slug contribute to cancer progression by mediating epithelial-mesenchymal transition (EMT), which results in tumor cell invasion and metastases. We extend this current understanding to demonstrate their involvement in the development of resistance to radiation and paclitaxel. The process is orchestered through the acquisition of a novel subset of gene targets that are repressed under conditions of stress, effectively inactivating p53-mediated apoptosis, while another subset of targets continues to mediate EMT. Repressive activities are complemented by a concurrent de-repression of specific genes resulting in the acquisition of stem cell--like characteristics. Such cells are bestowed with three critical capabilities viz. EMT, resistance to p53-mediated apoptosis and a self-renewal program, that together define the functionality and survival of metastatic Cancer Stem Cells (CSCs). EMT provides a mechanism of escape to a new, less adverse niche, resistance to apoptosis ensures cell survival in conditions of stress in the primary tumor; while acquisition of 'stemness' ensures generation of the critical tumor mass required for progression of micro- to macro-metastases. Our findings, besides achieving considerable expansion of the inventory of direct genes targets, more importantly demonstrate that such elegant cooperative modulation of gene regulation mediated by Snail and Slug is critical for a cancer cell to acquire stem cell characteristics towards resisting radio- or chemotherapy mediated cellular stress, and this may be a determinative aspect of aggressive cancer metastases.
PMID: 19544473 [PubMed - as supplied by publisher

06-24-2009, 04:31 PM	#30
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	1: Stem Cells. 2009 Jun 18. [Epub ahead of print] Snail and Slug mediate radio- and chemo-resistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY, Bapat SA. National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind, Pune 411 007, INDIA. The transcriptional repressors Snail and Slug contribute to cancer progression by mediating epithelial-mesenchymal transition (EMT), which results in tumor cell invasion and metastases. We extend this current understanding to demonstrate their involvement in the development of resistance to radiation and paclitaxel. The process is orchestered through the acquisition of a novel subset of gene targets that are repressed under conditions of stress, effectively inactivating p53-mediated apoptosis, while another subset of targets continues to mediate EMT. Repressive activities are complemented by a concurrent de-repression of specific genes resulting in the acquisition of stem cell--like characteristics. Such cells are bestowed with three critical capabilities viz. EMT, resistance to p53-mediated apoptosis and a self-renewal program, that together define the functionality and survival of metastatic Cancer Stem Cells (CSCs). EMT provides a mechanism of escape to a new, less adverse niche, resistance to apoptosis ensures cell survival in conditions of stress in the primary tumor; while acquisition of 'stemness' ensures generation of the critical tumor mass required for progression of micro- to macro-metastases. Our findings, besides achieving considerable expansion of the inventory of direct genes targets, more importantly demonstrate that such elegant cooperative modulation of gene regulation mediated by Snail and Slug is critical for a cancer cell to acquire stem cell characteristics towards resisting radio- or chemotherapy mediated cellular stress, and this may be a determinative aspect of aggressive cancer metastases. PMID: 19544473 [PubMed - as supplied by publisher