Epithelial–mesenchymal transition in cancer development and its clinical significance

Abstract

The epithelial-mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2010; 101: 293-299) D evelopment of distant metastases is the final stage of solid cancer progression and is responsible for the majority of cancer-related deaths.(1) Distant metastasis alone or with concurrent locoregional recurrence accounts for nearly 80% of all first relapses in women with breast cancer.(2) While clinically of great importance, the biology of metastasis remains unsolved. The process of tumor metastasis consists of multiple steps, all of which are required to achieve tumor spreading.(3,4) First, cancer cells escape from the primary tumor site. Next, cancer cells invade the tumor stroma and enter the blood circulation directly or the lymphatic system via intravasation. Most circulating cancer cells undergo apoptosis due to anoikis conditions.(5) If cancer cells survive in circulation they may reach more suitable sites by attaching to endothelial cells and extravasating from the circulation into the surrounding tissues. Finally, distal colonization requires that cancer cells invade and grow in the new environment.Recently, the concept of the epithelial-mesenchymal transition (EMT), as developed in the field of embryology, has been extended to cancer progression and metastasis.(6,7) In vitro and experimental animal model data now support the role of EMT in metastasis, concepts supported by analyses of clinical samples. Indeed, the biology of EMT has been clarified in tumor samples through use of EMT-associated markers, such as mesenchymalspecific markers (i.e. vimentin and fibronectin), (8,9) epithelial specific markers (i.e. E-cadherin and cytokeratin), (10,11) and transcription factors (i.e. SNAIL and SLUG). (12) Most recently, several intriguing studies have described the novel mechanism underlying EMT activation. In the current study, we will discuss the role of small non-coding RNA (micro-RNA) in regulating EMT-r...

DDAH1 mediates gastric cancer cell invasion and metastasis via Wnt/β‐catenin signaling pathway

“…EMT is associated with dissemination of cancer, thereby facilitating tumor progression (Brabletz, 2012; Iwatsuki et al ., 2010). During EMT, cancer cells decrease cell–cell junctions and gain the mesenchymal characteristics, thus enhancing their abilities of migration and invasiveness (Thiery, 2002; Thiery et al ., 2009).…”

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

“…During tumor progression, some CSCs undergo EMT and acquire the ability to infiltrate surrounding tissues and metastasize (Thiery et al, 2002). EMT occurs when the cells are dissociated from each other, lose the expression of epithelial markers and earn the expression of mesenchymal markers, and change their polarization and cytoskeletal structure to establish new cell-matrix interactions (Iwatsuki et al, 2010) (Key features of EMT are summarized in Table 1).…”

Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer

“…Epithelial and mesenchymal cells have different phenotypes and functions. Epithelial cells express high level of E-cadherin, while the proteins including N-cadherin, fibronectin and vimentin are overexpressed in mesenchymal cells (29,30). During cancer progression, the transition of epithelial cells into mesenchymal cells is always observed.…”