Epithelial–mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features. In cancer, EMT is associated with tumor initiation, invasion, metastasis, and resistance ...to therapy. Recently, it has been demonstrated that EMT is not a binary process, but occurs through distinct cellular states. Here, we review the recent studies that demonstrate the existence of these different EMT states in cancer and the mechanisms regulating their functions. We discuss the different functional characteristics, such as proliferation, propagation, plasticity, invasion, and metastasis associated with the distinct EMT states. We summarize the role of the transcriptional and epigenetic landscapes, gene regulatory network and their surrounding niche in controlling the transition through the different EMT states.
EMT occurs through distinct intermediate states in vivo.
Distinct EMT transition states can be identified using cell surface markers and single-cell RNA-sequencing.
Distinct EMT transition states present different functions, with the hybrid EMT state presenting the highest metastatic potential.
Distinct EMT transition states present different gene expression and chromatin landscape.
Distinct EMT transition states are localized in different niches that regulate cell fate transitions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although many genes that lead to different types of cancer when mutated have been identified, the cells that initiate tumour formation following accumulation of these mutations have, until recently, ...remained elusive. This review explores how mouse genetic lineage-tracing experiments that allow the expression of oncogenes and/or the deletion of tumour suppressor genes in defined cell lineages have been instrumental in defining the cellular origin of different solid tumours in mouse models for various human cancers.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Different mechanisms contribute to intratumor heterogeneity, including genetic mutations, the microenvironment, and the existence of subpopulations of cancer cells with increased renewal capacity and ...the ability to recapitulate the heterogeneity found in primary tumors, which are referred to as cancer stem cells (CSCs). In this review, we discuss how the concept of CSCs has been defined, what assays are currently used to define the functional properties of CSCs, what intrinsic and extrinsic mechanisms regulate CSC functions, how plastic CSCs are, and the importance of epithelial-to-mesenchymal transition in conferring CSC properties. Finally, we discuss the mechanisms by which CSCs may resist medical therapy and contribute to tumor relapse.
The versatility of epithelial stem cells
Stem cells are very important in the maintenance of our bodies' tissues and organs. Blanpain and Fuchs review how different populations of naturally ...lineage-restricted epithelial stem cells and committed progenitors can also display remarkable plasticity. These cells can reacquire long-term self-renewing capacities and multilineage differentiation potential during physiological and regenerative conditions. These abilities depend on whether the stem cell remains within its resident niche or has been mobilized to repair a wound. Such cellular plasticity has implications for regenerative medicine and for cancer.
Science
, this issue p.
10.1126/science.1242281
Tissues rely upon stem cells for homeostasis and repair. Recent studies show that the fate and multilineage potential of epithelial stem cells can change depending on whether a stem cell exists within its resident niche and responds to normal tissue homeostasis, whether it is mobilized to repair a wound, or whether it is taken from its niche and challenged to de novo tissue morphogenesis after transplantation. In this Review, we discuss how different populations of naturally lineage-restricted stem cells and committed progenitors can display remarkable plasticity and reversibility and reacquire long-term self-renewing capacities and multilineage differentiation potential during physiological and regenerative conditions. We also discuss the implications of cellular plasticity for regenerative medicine and for cancer.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Tissue repair is critical for animal survival. The skin epidermis is particularly exposed to injuries, which necessitates rapid repair. The coordinated action of distinct epidermal stem cells ...recruited from various skin regions together with other cell types, including fibroblasts and immune cells, is required to ensure efficient and harmonious wound healing. A complex crosstalk ensures the activation, migration and plasticity of these cells during tissue repair.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The maintenance and repair of many adult tissues are ensured by stem cells (SCs), which reside at the top of the cellular hierarchy of these tissues. Functional assays, such as in vitro clonogenic ...assays, transplantation and in vivo lineage tracing, have been used to assess the renewing and differentiation potential of normal SCs. Similar strategies have suggested that solid tumours may also be hierarchically organized and contain cancer SCs (CSCs) that sustain tumour growth and relapse after therapy. In this Opinion article, we discuss the different parallels that can be drawn between adult SCs and CSCs in solid tumours.
Tissues rely upon stem cells for homeostasis and repair. Recent studies show that the fate and multilineage potential of epithelial stem cells can change depending on whether a stem cell exists ...within its resident niche and responds to normal tissue homeostasis, whether it is mobilized to repair a wound, or whether it is taken from its niche and challenged to de novo tissue morphogenesis after transplantation. In this Review, we discuss how different populations of naturally lineage-restricted stem cells and committed progenitors can display remarkable plasticity and reversibility and reacquire long-term self-renewing capacities and multilineage differentiation potential during physiological and regenerative conditions. We also discuss the implications of cellular plasticity for regenerative medicine and for cancer.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Squamous cell carcinomas (SCCs) are among the most prevalent human cancers. SCC comprises a wide range of tumours originated from diverse anatomical locations that share common genetic mutations and ...expression of squamous differentiation markers. SCCs arise from squamous and non-squamous epithelial tissues. Here, we discuss the different studies in which the cell of origin of SCCs has been uncovered by expressing oncogenes and/or deleting tumour suppressor genes in the different cell lineages that compose these epithelia. We present evidence showing that the squamous differentiation phenotype of the tumour depends on the type of mutated oncogene and the cell of origin, which dictate the competence of the cells to initiate SCC formation, as well as on the aggressiveness and invasive properties of these tumours.
The skin epidermis and its array of appendages undergo ongoing renewal by a process called homeostasis. Stem cells in the epidermis have a crucial role in maintaining tissue homeostasis by providing ...new cells to replace those that are constantly lost during tissue turnover or following injury. Different resident skin stem cell pools contribute to the maintenance and repair of the various epidermal tissues of the skin, including interfollicular epidermis, hair follicles and sebaceous glands. Interestingly, the basic mechanisms and signalling pathways that orchestrate epithelial morphogenesis in the skin are reused during adult life to regulate skin homeostasis.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Epidermal stem cells of the skin Blanpain, Cédric; Fuchs, Elaine
Annual review of cell and developmental biology,
01/2006, Volume:
22
Journal Article
Peer reviewed
Open access
The skin constantly renews itself throughout adult life, and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the epidermis and hair follicle ...ensure the maintenance of adult skin homeostasis and hair regeneration, but they also participate in the repair of the epidermis after injuries. We summarize here the current knowledge of epidermal SCs of the adult skin. We discuss their fundamental characteristics, the methods recently designed to isolate these cells, the genes preferentially expressed in the multipotent SC niche, and the signaling pathways involved in SC niche formation, SC maintenance, and activation. Finally, we speculate on how the deregulation of these pathways may lead to cancer formation.
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