Landscape perspectives of tumor, EMT, and development.

A tumor is rarely fatal until becoming metastatic. Recent discoveries suggest that epithelial mesenchymal transition(EMT) is an important process which contributes to not only cancer metastasis but also increased stemness. Cancer cells with stem cell characteristics are called cancer stem cells (CSCs). We review recent efforts to quantify and delineate the relationship among EMT, CSC and tumor development. When the gene regulatory network is tightly regulated through the effectively fast regulatory binding, Cancer, Premalignant, Normal, CSC, stem cell (SC), Lesion and Hyperplasia states emerged. The corresponding landscape topography for all of these states can be quantified to a global way for uncovering the relationship among the tumor, metastasis, and development. On the other hand, phenotypic and functional heterogeneity is regarded as one of the greatest challenge in cancer treatment. Cancer and CSCs are heterogeneous and give rise to tumorigenic and non-tumorigenic cells during self-renewal, differentiation and epigenetic diversification. Further, if the gene regulatory network is weakly regulated through the effective slow regulatory binding (by DNA methylation or histone modification etc), multiple meta-stable states can emerge. This model can provide an epigenetic and physical rather than genetic and fixed origin of heterogeneity. Elucidating the origin of and dynamic nature of tumor cells will likely help better understand the cellular basis of therapeutic response, resistance, and relapse.