Mammary Gland Studies as Important Contributors to the Cause of Epithelial Mesenchymal Plasticity in Malignancy

Abstract

Over the last few years, the field of epithelial-mesenchymal transition (EMT) has rapidly expanded, both in developmental biology and in disease pathology (Fig. 1a). The growing literature suggests that this field may perhaps more appropriately be referred to as epithelial-mesenchymal plasticity (EMP), in light of the increased evidence for the reverse transition (MET), and for the ‘hybrid state’, in which cells express both epithelial and mesenchymal markers. Breast cancer research has always been well represented in the cancer EMT literature (Fig. 1b) and studies of EMT in normal mammary function that may relate to tumour biology are emerging and are adding to the total number of mammaryrelated EMT papers (Fig. 1c). This Special Issue entitled “EMT in Mammary Development and Breast Cancer Progression” captures much of the current themes in mammary biology and EMP, arranged somewhat chronologically. It begins with a description of the EMT programs utilized in embryologic development (Ford and colleagues), then moves on to polarity mechanisms and the ways in which these are regulated during developmental EMT (Humbert and colleagues), followed by a detailed description of EMT regulation by the SNAIL family of developmental transcription factors (Garcia-de Hererros and Savagner). It then continues with a historical perspective of EMT and a description of some of the mouse mammary models that exhibit EMT (Cardiff). Following this perspective, the special issue moves into the regulation of EMT by growth factors including the TGF-β (Schiemann and colleagues) and EGF (Strizzi and colleagues) families, as well as the regulation of EMT by other critical players, including MMPs (Radisky) and the fascinating and more recently described microRNAs (miRs; Goodall and colleagues). In the final set of articles within this special issue, the relationship between EMP and the breast cancer stem cell (BCSC) phenotype (Thompson and colleagues) is discussed, including the clinical implications of this connection that have been so revealing of late (Rosen and colleagues). This leads directly into the last article of the issue, in which the prospect of EMT in the circulating tumour cells (CTC) that predispose patients to metastasis is discussed (Gilles and colleagues). It is heartening that several authors took up the suggestion to invite other leaders with similar interests to join their article, as seen with Garcia-de Hererros and Savagner on Snail, Goodall and Richer on miRs, Thompson, Mani and Weinberg on BCSC and Gilles and Thompson on relationships between EMP and CTC. This is not always easy, and we thank these authors for their willingness to participate in this manner and to effectively broaden the scope of this collection further than could have otherwise been done due to issue size limitations. Certainly such arrangements result in a more comprehensive and balanced review of the current literature. In addition to their specific focus, many of the authors provide their slightly different description of current issues H. L. Ford (*) Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO, USA e-mail: Heide.Ford@ucdenver.edu