Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

Epithelial-to-mesenchymal transition (EMT) confers primary resistance to trastuzumab (Herceptin)

“…Considering that bona fide mammospheres are non-adherent spherical cell clusters enriched in mammary stem/progenitor cells, it is intriguing that the steady depletion of CD44 + CD24 -/low mesenchymal cells in response to the specific knockdown of SLUG/SNAIL2 does not affect the epithelial nature of the mammospheres generated by designated as the CSC subpopulation of breast cancer cells that is enriched in tumorigenic cells. 3,[54][55][56] Accordingly, it might be reasonable to conclude that the aberrant expression of the EMT transcription factor SLUG/SNAIL2 biases HER2 + basal epithelial cells toward a highly tumorigenic CSC-like mesenchymal fate that is unresponsive to trastuzumab. Alternatively, the CSCs may not be considered distinct entities, but rather tumor cells that transiently acquire or lose stem cell-like properties as a consequence of EMT regulation.…”

Metabolic reprogramming of the tumor

“…EMT provokes loss of connection to other cells and changes their morphology, from an epithelial-to a fibroblast-like structure (Thiery, 2002;Thiery and Sleeman, 2006;Thiery et al, 2009;Cannito et al, 2010). This process is reversible; such cells are able to regenerate the bulk-like character of their tumors of origin after metastasis (Pinner et al, 2009;Floor et al, 2011).…”

Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

“…At the initial stage of tumorigenesis, intrinsic and extrinsic factors cause intracellular genetic mutations and epigenetic alterations, resulting in generation of oncogenes that induce the production of CSCs and tumorigenesis [6]. The CSCs can be produced from precancerous stem cells [59][60][61][62][63][64], cell de-differentiation [65], or an epithelial-mesenchymal transition [66][67][68]. Malignant mesenchymal stem cells have been found in the niche of cancers [66,67], and an epithelial-mesenchymal transition may be an early key step in the initiation of TME and tumorigenesis [68].…”

“…First, CSCs actively participate in the development of the CSC niche [11]. Second, CSCs may trans-differentiate into cancer-associated stromal cells [58][59][60][61][62][65][66][67][68][69], such as cancer-associated fibroblasts and tumor endothelial cells [70,71]. The CSC-differentiated tumor endothelial cells are important in tumor neovascularization and the genesis of TME [72][73][74][75].…”

“…First, precancerous cells are reversible and may be induced to regress to normal cells, depending on the environmental cue [59][60][61]. Second, oncogenic mesenchymal stem cells could be reversed to normal epithelial cells using the approach of mesenchymalepithelial transition, because epithelial-mesenchymal transition may be reversible [65][66][67][68]. Furthermore, differentiation of CSCs and inhibition of the proliferation of these cells by changes in environmental cues may be additional options to normalize malignant TME.…”