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About the Authors:
Archana Dhasarathy
Affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, United States of America
Dhiral Phadke
Affiliation: SRA International Inc., Research Triangle Park, North Carolina, United States of America
Deepak Mav
Affiliation: SRA International Inc., Research Triangle Park, North Carolina, United States of America
Ruchir R. Shah
Affiliation: SRA International Inc., Research Triangle Park, North Carolina, United States of America
Paul A. Wade
* E-mail: [email protected]
Affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, United States of America
Introduction
Breast cancer is the most frequently diagnosed malignancy in women worldwide [reviewed in [1]]. In recent years, prognosis for breast cancer has improved as a result of advances in diagnosis and treatment. Nevertheless, tumor dormancy after treatment followed by local, regional or distant recurrence is a leading cause of breast cancer mortality [reviewed in [1]]. Clinically, advanced-stage breast cancer is characterized by metastasis, a multi-step process postulated to involve cancer cell invasion, proliferation, and eventual survival in distant tissues following transport by the circulatory system [1]. An early developmental phenomenon known as ‘Epithelial to Mesenchymal Transition’ or EMT, which results in the acquisition of an invasive, mesenchymal phenotype by epithelial cells, has been postulated to play an important role in cancer metastasis [reviewed in [2]]. Recently, cell-fate mapping strategies in mouse models of mammary tumors [3] provided direct evidence for EMT.
Several proteins that are involved in EMT during early embryonic development have come under close scrutiny in cancer cell programs. In particular, the role of the Snail family of zinc finger proteins in EMT and cancer has been highlighted in several publications [reviewed in [4]]. These proteins effect changes in gene expression that are required for such important developmental processes like mesoderm formation, left-right identity and cell fate decisions [reviewed in [4]]. Responding to environmental cues, the highly related transcriptional repressors Snail (SNAI1) and Slug (SNAI2) are thought to act as master regulators, altering expression of a number of genes including E-cadherin (CDH1) [4], [5], [6], and contribute to physiological changes resulting in EMT [4], [7].
Despite the many similarities between Snail and Slug, there are clear differences in their biological functions. Combinatorial depletion...