Snail and Slug Mediate Radioresistance and Chemoresistance by Antagonizing p53‐Mediated Apoptosis and Acquiring a Stem‐Like Phenotype in Ovarian Cancer Cells

By N. Kurrey, S. Jalgaonkar, Alok V. Joglekar, Avinash D. Ghanate, P. Chaskar, Rahul Y. Doiphode, S. Bapat. Stem Cells, 2009

641 citations recorded by the source corpus.

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 orchestrated through the acquisition of a novel subset of gene targets that is 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 derepression of specific genes resulting in the acquisition of stem cell‐like characteristics. Such cells are bestowed with three critical capabilities, namely EMT, resistance to p53‐mediated apoptosis, and a self‐renewal program, that together define the functionality and survival of metastatic cancer stem cells. 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; whereas acquisition of “stemness” ensures generation of the critical tumor mass required for progression of micrometastases to macrometastases. 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 toward resisting radiotherapy‐ or chemotherapy‐mediated cellular stress, and this may be a determinative aspect of aggressive cancer metastases. STEM CELLS 2009;27:2059–2068

Subfields: Biomedical Engineering, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/c05f203f5bc45a106e88af331fdf3fc25e9f2e95

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Citations in the corpus

Dynamic EMT: a multi‐tool for tumor progression (2021, positive): “SLUG and SNAIL contribute to evading therapy-induced apoptosis by interfering with p53 function, repression of the tumor-suppressor PTEN , or upregulation of the pro-survival protein BCL-XL (Vega et al , 2004; Escriva et al , 2008; Kurrey et al , 2009; Wu et al , 2015; Cao et al , 2016).”
Anoikis molecular pathways and its role in cancer progression. (2013, background): “p53-mediated apoptosis, promoted by Snail-1, Slug, or Hedgehog signaling [134].”
The ins and outs of the epithelial to mesenchymal transition in health and disease. (2011, background): “Snail factors confer radioresistance and chemoresistance by antagonizing p53-mediated apoptosis (Kurrey et al. 2009).”
Epithelial-mesenchymal transitions in development and disease. (2009, background): “Similarly, Snail also confers resistance to paclitaxel, adriamycin, and radiation by antagonizing p53-mediated apoptosis (Kajita et al., 2004; Kurrey et al., 2009) (Figure 6A).”
Drug resistance and combating drug resistance in cancer (2019, background): “It was shown that transcriptional repressors Snail and Slug not only mediate EMT, but also resistance to p53 induced apoptosis, and a self-renewal program[19].”
EMERGING BIOLOGICAL PRINCIPLES OF METASTASIS (2017, positive): “…to elevate the resistance of carcinoma cells to various types of cytotoxic treatments, including both radio- and chemotherapies (Gupta et al., 2009; Kurrey et al., 2009), providing one explanation of the often-observed phenomenon that CSCs tend to be more therapyresistant than their non-CSC…”
The Role of Snail in EMT and Tumorigenesis (2013, background): “These two molecules indirectly increase the activation of a self-renewal program by up-regulating NANOG, HDAC1, TCF4, KLF4, HDAC3 and GPC3, and further induce expression of other pluripotency activators including OCT4, BMI1 and Nestin; as well as increase the number of cells with CD44+CD117+, which ”