Recent studies also have showed that overexpression of these EMT-related transcription factors can also induce a CD44-high/CD24-low pattern on epithelial cells, which is associated with the somatic selleck products cells obtaining stem cell and CSC properties (Mani et al, 2008). Metastatic potential depends on multiple factors that determine overall tumour cell growth, survival, angiogenesis, and invasion. For epithelial malignancies, the EMT is considered to be a crucial event in the metastatic process, which involves disruption of epithelial cell homoeostasis and the acquisition of a migratory mesenchymal phenotype. The EMT appears to be controlled by canonical pathways such as the Wnt and transforming growth factor �� pathways, both of which can be aberrantly activated during neoplasia.

A recent report suggests that there may be a direct link between the EMT and acquisition of stem cell properties (Mani et al, 2008). In this study, we found that many diverse lines of evidence suggest a possible link between CD44, CSCs, the sphere-forming culture, and tumour metastasis. During the process of tumour metastasis, lipid raft-associated CD44 is required for survival in the suspension condition, and then nuclear CD44/acetylated-STAT3 generates cells with properties of CSCs and the EMT phenotype by transcriptional reprogramming, leading to drug resistance, tumour metastasis, and a resulting poor prognosis. The observations in this study have important implications, as they propose to indicate that targeting of CD44 might be key to interfering with the formation and spread of cancers.

This study, for the first time, will demonstrate the role of CD44 in tumour metastasis by using a model where multiple phenotypic cancer cell subpopulations coexist in a dynamic equilibrium and where the tumourigenic and metastatic properties of cell subsets, including CSCs, can be tested concurrently, trying to chart their functional and hierarchical relationships. Results CD44 leading to stable changes in cell ability and morphology after the suspension culture In this study, we tested whether the transcriptional reprogramming led by nuclear CD44 has an active role in transforming cancer cells to a CSC-like phenotype. First, we analysed the expression patterns of the CSC surface marker CD44 using fluorescence-activated cell sorting (FACS) for the following six human colon cancer cell lines: COLO 205, COLO 320, HCT-116, HT29, DLD-1, and LoVo cells. As shown in Supplementary Figure S1, COLO 205, COLO 320, and HCT-116 cells showed a high level of CD44 expression, with up to 90% of cells Brefeldin_A expressing CD44, whereas HT29, DLD-1, and LoVo cells showed as little as 70% expression. We fractionated HT29 and DLD-1 cells by FACS into CD44+ and CD44? cell fractions.