Cancer stem cell theory: Are we moving past the mist?

Cancer stem cells (CSC) are a subpopulation of tumor cells that have superior capacities of self-renewal, metastatic dissemination, and chemo-resistance. These characteristics resemble, to some extent, the outcome of certain biological processes, including epithelial-mesenchymal transition (EMT), autophagy, and cellular stress response. Indeed, it has been shown that the stimuli that induce these processes and CSC are overlapping, and CSC and tumor cells that underwent EMT or autophagy are much alike. However, as the crosstalk between CSC, EMT, autophagy, and cellular stress is further explored, these processes are also found to have an opposing role in CSC, depending on condition and status of cells. This contextual effect is likely due to overwhelming reliance on CSC markers for their identification, and/or discrepancies in recognition of CSC as a particular cell population or cellular state. In this review, we will summarize how EMT, autophagy, and cellular stress response are tied or unwound with CSC. We will also discuss the current view of CSC theory evolved from the emphasis of heterogenicity and plasticity of CSC.