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2019 marks twenty years since the launch of Nature Cell Biology. To celebrate our 20th anniversary we present a Focus of specially commissioned Review and Perspective articles that discuss topics across the diverse areas covered by the journal. These pieces are accompanied by a Collection of research articles published in Nature Cell Biology over the last two decades. Although they are not intended to be comprehensive, these commissioned pieces and research articles highlight the rich history and diverse scope of the journal.
Cancer-associated fibroblasts (CAFs) promote metastasis by creating tracks for cancer cell migration. Labernadie et al. now show that heterotypic adhesions between E-cadherin on cancer cells and N-cadherin on CAFs transmit forces to drive invasion.
Aguirre-Ghiso and colleagues report that hypoxia in the primary tumour microenvironment leads to upregulation of a dormancy signature in the tumour cells that persists after their dissemination to distant sites, permitting them to evade therapy.
Yang and colleagues identify a lncRNA that controls HIF1α signalling to stabilize HIF1α under normoxic conditions, and promotes breast cancer tumorigenesis.
Gottlieb and colleagues demonstrate that glioblastoma cell proliferation under glutamine starvation conditions depends on the glutamine-synthetase-dependent conversion of glutamate to glutamine to fuel purine biosynthesis and cell growth.
Rodeheffer and colleagues show that a high-fat diet in mice activates Akt2 signalling in adipocyte precursors within white adipose tissue deposits, leading to their proliferation and differentiation into adipocytes, and to obesity.
Yang and colleagues report that increased extracellular matrix stiffness promotes nuclear localization of Twist1 to drive epithelial–mesenchymal transition, cancer cell invasion and metastasis.
Brown adipose cells contribute to body temperature maintenance by converting lipids and glucose into heat, and can be found in white adipose tissue. Wolfrum and colleagues find a population of cells in white adipose tissue that can adopt brown or white characteristics in response to cold.
Sahai and colleagues report that YAP is required for the establishment and function of cancer-associated fibroblasts. They propose that matrix stiffening promotes Src-mediated activation of YAP in fibroblasts, which is necessary for the cancer-associated fibroblast phenotype and further promotes matrix stiffening in a positive feedback loop.
Werb and colleagues demonstrate that GATA3, a transcription factor that promotes luminal differentiation in the mammary gland, suppresses breast cancer metastasis to the lung by upregulating miR-29b. This microRNA suppresses pro-metastatic characteristics, including mesenchymal traits and the expression of microenvironmental factors involved in angiogenesis and extracellular matrix remodelling.
Bissell, Ghajar and colleagues use organotypic culture systems and in vivo mouse and zebrafish models to reveal the distinct effects of different microvascular niches on tumour cell dormancy. They report that although the stable microvasculature promotes cancer cell quiescence through the production of thrombospondin-1, cancer cells residing near neovascular tips are induced to grow through the action of TGF-β and periostin.
Dimmeler and colleagues show that the atheroprotective transcription factor KLF2 activates expression of the microRNAs miR-143/145 in endothelial cells. miR-143/145 are subsequently enriched in secreted microvesicles and taken up by smooth muscle cells to elicit anti-atherogenic responses.
Del Sal and colleagues demonstrate that the YAP and TAZ effectors of the Hippo pathway are under the control of the mevalonate pathway. They show that mutant p53 and SREBP-dependent activation of mevalonate signalling activates YAP and TAZ and promotes tumour formation in mice, a growth phenotype also conserved in Drosophila.
Following skeletal muscle damage, a population of resident fibro/adipogenic progenitors (FAP) initiates proliferation, resulting in the generation of ectopic white fat but not myofibres. FAPs enhance the differentiation of the myogenic progenitors involved in muscle regeneration.
Cells at the origin of tumour initiation are unknown for many cancers. In hedgehog-induced basal cell carcinoma, skin hair-follicle stem cells do not participate to tumorigenesis, whereas Hedgehog activation in stem cells from the interfollicular epidermis does induce malignancy.
miRNAs can both promote and repress tumorigenesis, and directly control epithelial–mesenchymal transition (EMT). miR-9 (which is upregulated in breast cancer cells) is activated by MYC and MYCN, and regulates EMT and metastasis through direct control of E-cadherin. In contrast, tumour angiogenesis is controlled indirectly through effects on vascular endothelial growth factor (VEGF) expression.
Cancer stem cell activity may not merely be an intrinsic characteristic of a subset of cancer cells and could be regulated by environmental cues. High Wnt activity in human colorectal cancer designates a tumour-initiating population and is orchestrated by the microenvironment.
Administration of spermidine, a polyamine whose concentration declines during ageing, extends lifespan in yeast, flies, worms and in human immune cells. Spermidine prevents early oxidative stress and necrotic cell death and increases the expression of autophagy genes by inhibiting histone acetyltransferases action on histone H3.
Intracellular tau inclusions, a hallmark of several neurodegenerative diseases, propagate in the brain in an unknown fashion. Brain extracts prepared from mice expressing mutated human tau injected into mice expressing wild-type human tau induce the formation and spread of wild-type human tau inclusions.
The epithelial-to-mesenchymal transition transcription factor ZEB1 is involved in metastasis. It is now shown to regulate the tumour-initiating capacity of pancreatic and colorectal cancer cells, through the repression of the stemness-inhibiting miR200s, which are found to inhibit the polycomb repressor Bmi-1.
Human glioblastoma cells release microvesicles containing a diverse set of proteins, miRNAs and mRNAs, which can be taken up by normal host cells that translate the mRNA. Glioma-derived microvesicles carrying the specific tumour markers EGFRvIII and miRNA-21 promote cell proliferation and may serve as a diagnostic tool.