A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma
01 May 2017-
About: The article was published on 2017-05-01 and is currently open access. It has received 139 citations till now. The article focuses on the topics: Wnt signaling pathway & Adenocarcinoma.
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TL;DR: The core Wnt/β-catenin signaling pathway is described, how it controls stem cells, and contributes to disease, and strategies for Wnt-based therapies are discussed.
2,663 citations
TL;DR: It is highlighted how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state which could function as cancer stem cells, and its effects on the immunobiology of carcinomas.
Abstract: Epithelial–mesenchymal transition (EMT) is a cellular programme that is known to be crucial for embryogenesis, wound healing and malignant progression. During EMT, cell–cell and cell–extracellular matrix interactions are remodelled, which leads to the detachment of epithelial cells from each other and the underlying basement membrane, and a new transcriptional programme is activated to promote the mesenchymal fate. In the context of neoplasias, EMT confers on cancer cells increased tumour-initiating and metastatic potential and a greater resistance to elimination by several therapeutic regimens. In this Review, we discuss recent findings on the mechanisms and roles of EMT in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this programme. We also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. In addition, we describe the contributions of the tumour microenvironment in inducing EMT and the effects of EMT on the immunobiology of carcinomas. Epithelial–mesenchymal transition (EMT) is crucial for embryogenesis, wound healing and cancer development, and confers greater resistance to cancer therapies. This Review discusses the mechanisms of EMT and its roles in normal and neoplastic tissues, the contribution of cell-intrinsic signals and the microenvironment to inducing EMT, and its effects on the immunobiology of carcinomas.
1,949 citations
TL;DR: New developments in the cancer stem cell field are discussed in relationship to changing insights into how normal stem cells maintain healthy tissues and the first successes of therapies based on the CSC concept are emerging.
Abstract: The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their identification and eradication has not been as obvious as was initially hoped. Recently developed lineage-tracing and cell-ablation strategies have provided insights into CSC plasticity, quiescence, renewal, and therapeutic response. Here we discuss new developments in the CSC field in relationship to changing insights into how normal stem cells maintain healthy tissues. Expectations in the field have become more realistic, and now, the first successes of therapies based on the CSC concept are emerging.
1,686 citations
TL;DR: In this paper, the authors provide evidence that local microbiota provoke inflammation associated with lung adenocarcinoma by activating lung resident γδ T cells, and link local microbiota-immune crosstalk to lung tumor development and define key cellular and molecular mediators that may serve as effective targets in lung cancer intervention.
494 citations
TL;DR: It is shown that the rare AT2 lung stem cells have a special niche next to a fibroblast secreting Wnts, and many of them are near single, Wnt-expressing fibroblasts, which maintains the gas exchange surface and is coopted in cancer.
Abstract: Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete surfactant Rare AT2s also function as alveolar stem cells We show that AT2 lung stem cells display active Wnt signaling, and many of them are near single, Wnt-expressing fibroblasts Blocking Wnt secretion depletes these stem cells Daughter cells leaving the Wnt niche transdifferentiate into AT1s: Maintaining Wnt signaling prevents transdifferentiation, whereas abrogating Wnt signaling promotes it Injury induces AT2 autocrine Wnts, recruiting "bulk" AT2s as progenitors Thus, individual AT2 stem cells reside in single-cell fibroblast niches providing juxtacrine Wnts that maintain them, whereas injury induces autocrine Wnts that transiently expand the progenitor pool This simple niche maintains the gas exchange surface and is coopted in cancer
486 citations
References
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TL;DR: The Integrative Genomics Viewer (IGV) is a high-performance viewer that efficiently handles large heterogeneous data sets, while providing a smooth and intuitive user experience at all levels of genome resolution.
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6,930 citations