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Nature Cell Biology

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https://www.readbyqxmd.com/read/28218910/a-mechanically-active-heterotypic-e-cadherin-n-cadherin-adhesion-enables-fibroblasts-to%C3%A2-drive-cancer-cell-invasion
#1
Anna Labernadie, Takuya Kato, Agustí Brugués, Xavier Serra-Picamal, Stefanie Derzsi, Esther Arwert, Anne Weston, Victor González-Tarragó, Alberto Elosegui-Artola, Lorenzo Albertazzi, Jordi Alcaraz, Pere Roca-Cusachs, Erik Sahai, Xavier Trepat
Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218909/a-twist2-dependent-progenitor-cell-contributes-to-adult-skeletal-muscle
#2
Ning Liu, Glynnis A Garry, Stephen Li, Svetlana Bezprozvannaya, Efrain Sanchez-Ortiz, Beibei Chen, John M Shelton, Priscilla Jaichander, Rhonda Bassel-Duby, Eric N Olson
Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2(+) progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218908/cell-matrix-signals-specify-bone-endothelial-cells-during-developmental-osteogenesis
#3
Urs H Langen, Mara E Pitulescu, Jung Mo Kim, Rocio Enriquez-Gasca, Kishor K Sivaraj, Anjali P Kusumbe, Amit Singh, Jacopo Di Russo, M Gabriele Bixel, Bin Zhou, Lydia Sorokin, Juan M Vaquerizas, Ralf H Adams
Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. While a specialized capillary subtype, termed type H, has been recently shown to couple angiogenesis and osteogenesis in adolescent, adult and ageing mice, little is known about the formation of specific endothelial cell populations during early developmental endochondral bone formation. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218907/the-link-a-lncrna-interacts-with-ptdins-3-4-5-p3-to%C3%A2-hyperactivate-akt%C3%A2-and-confer-resistance-to-akt%C3%A2-inhibitors
#4
Aifu Lin, Qingsong Hu, Chunlai Li, Zhen Xing, Guolin Ma, Cheng Wang, Jun Li, Yin Ye, Jun Yao, Ke Liang, Shouyu Wang, Peter K Park, Jeffrey R Marks, Yan Zhou, Jianwei Zhou, Mien-Chie Hung, Han Liang, Zhibin Hu, Hongbing Shen, David H Hawke, Leng Han, Yubin Zhou, Chunru Lin, Liuqing Yang
Phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3 or PIP3) mediates signalling pathways as a second messenger in response to extracellular signals. Although primordial functions of phospholipids and RNAs have been hypothesized in the 'RNA world', physiological RNA-phospholipid interactions and their involvement in essential cellular processes have remained a mystery. We explicate the contribution of lipid-binding long non-coding RNAs (lncRNAs) in cancer cells. Among them, long intergenic non-coding RNA for kinase activation (LINK-A) directly interacts with the AKT pleckstrin homology domain and PIP3 at the single-nucleotide level, facilitating AKT-PIP3 interaction and consequent enzymatic activation...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218906/differential-cytokine-contributions-of-perivascular-haematopoietic-stem-cell-niches
#5
Noboru Asada, Yuya Kunisaki, Halley Pierce, Zichen Wang, Nicolas F Fernandez, Alexander Birbrair, Avi Ma'ayan, Paul S Frenette
Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28192422/identification-of-quiescent-and-spatially-restricted-mammary-stem-cells-that-are-hormone-responsive
#6
Nai Yang Fu, Anne C Rios, Bhupinder Pal, Charity W Law, Paul Jamieson, Ruijie Liu, François Vaillant, Felicity Jackling, Kevin He Liu, Gordon K Smyth, Geoffrey J Lindeman, Matthew E Ritchie, Jane E Visvader
Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5(+) basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures...
February 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28192421/g1-cyclins-link-proliferation-pluripotency-and-differentiation-of-embryonic-stem-cells
#7
Lijun Liu, Wojciech Michowski, Hiroyuki Inuzuka, Kouhei Shimizu, Naoe Taira Nihira, Joel M Chick, Na Li, Yan Geng, Alice Y Meng, Alban Ordureau, Aleksandra Kołodziejczyk, Keith L Ligon, Roderick T Bronson, Kornelia Polyak, J Wade Harper, Steven P Gygi, Wenyi Wei, Piotr Sicinski
Progression of mammalian cells through the G1 and S phases of the cell cycle is driven by the D-type and E-type cyclins. According to the current models, at least one of these cyclin families must be present to allow cell proliferation. Here, we show that several cell types can proliferate in the absence of all G1 cyclins. However, following ablation of G1 cyclins, embryonic stem (ES) cells attenuated their pluripotent characteristics, with the majority of cells acquiring the trophectodermal cell fate. We established that G1 cyclins, together with their associated cyclin-dependent kinases (CDKs), phosphorylate and stabilize the core pluripotency factors Nanog, Sox2 and Oct4...
February 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28166192/insulin-like-signalling-to-the-maternal-germline-controls-progeny-response-to-osmotic-stress
#8
Nicholas O Burton, Tokiko Furuta, Amy K Webster, Rebecca E W Kaplan, L Ryan Baugh, Swathi Arur, H Robert Horvitz
In 1893 August Weismann proposed that information about the environment could not pass from somatic cells to germ cells, a hypothesis now known as the Weismann barrier. However, recent studies have indicated that parental exposure to environmental stress can modify progeny physiology and that parental stress can contribute to progeny disorders. The mechanisms regulating these phenomena are poorly understood. We report that the nematode Caenorhabditis elegans can protect itself from osmotic stress by entering a state of arrested development and can protect its progeny from osmotic stress by increasing the expression of the glycerol biosynthetic enzyme GPDH-2 in progeny...
February 6, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28114269/a-ror1-her3-lncrna-signalling-axis-modulates-the-hippo-yap-pathway-to-regulate-bone-metastasis
#9
Chunlai Li, Shouyu Wang, Zhen Xing, Aifu Lin, Ke Liang, Jian Song, Qingsong Hu, Jun Yao, Zhongyuan Chen, Peter K Park, David H Hawke, Jianwei Zhou, Yan Zhou, Shuxing Zhang, Han Liang, Mien-Chie Hung, Gary E Gallick, Leng Han, Chunru Lin, Liuqing Yang
Bone metastases remain a serious health concern because of limited therapeutic options. Here, we report that crosstalk between ROR1-HER3 and the Hippo-YAP pathway promotes breast cancer bone metastasis in a long noncoding RNA-dependent fashion. Mechanistically, the orphan receptor tyrosine kinase ROR1 phosphorylates HER3 at a previously unidentified site Tyr1307, following neuregulin stimulation, independently of other ErbB family members. p-HER3 Tyr1307 recruits the LLGL2-MAYA-NSUN6 RNA-protein complex to methylate Hippo/MST1 at Lys59...
January 23, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28114272/actin-dynamics-and-competition-for-myosin-monomer-govern-the-sequential-amplification-of-myosin-filaments
#10
Jordan R Beach, Kyle S Bruun, Lin Shao, Dong Li, Zac Swider, Kirsten Remmert, Yingfan Zhang, Mary A Conti, Robert S Adelstein, Nasser M Rusan, Eric Betzig, John A Hammer
The cellular mechanisms governing non-muscle myosin II (NM2) filament assembly are largely unknown. Using EGFP-NM2A knock-in fibroblasts and multiple super-resolution imaging modalities, we characterized and quantified the sequential amplification of NM2 filaments within lamellae, wherein filaments emanating from single nucleation events continuously partition, forming filament clusters that populate large-scale actomyosin structures deeper in the cell. Individual partitioning events coincide spatially and temporally with the movements of diverging actin fibres, suppression of which inhibits partitioning...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28114271/phenotypic-heterogeneity-of-disseminated-tumour-cells-is-preset-by-primary-tumour-hypoxic-microenvironments
#11
Georg Fluegen, Alvaro Avivar-Valderas, Yarong Wang, Michael R Padgen, James K Williams, Ana Rita Nobre, Veronica Calvo, Julie F Cheung, Jose Javier Bravo-Cordero, David Entenberg, James Castracane, Vladislav Verkhusha, Patricia J Keely, John Condeelis, Julio A Aguirre-Ghiso
Hypoxia is a poor-prognosis microenvironmental hallmark of solid tumours, but it is unclear how it influences the fate of disseminated tumour cells (DTCs) in target organs. Here we report that hypoxic HNSCC and breast primary tumour microenvironments displayed upregulation of key dormancy (NR2F1, DEC2, p27) and hypoxia (GLUT1, HIF1α) genes. Analysis of solitary DTCs in PDX and transgenic mice revealed that post-hypoxic DTCs were frequently NR2F1(hi)/DEC2(hi)/p27(hi)/TGFβ2(hi) and dormant. NR2F1 and HIF1α were required for p27 induction in post-hypoxic dormant DTCs, but these DTCs did not display GLUT1(hi) expression...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28114270/long-range-self-organization-of-cytoskeletal-myosin-ii-filament-stacks
#12
Shiqiong Hu, Kinjal Dasbiswas, Zhenhuan Guo, Yee-Han Tee, Visalatchi Thiagarajan, Pascal Hersen, Teng-Leong Chew, Samuel A Safran, Ronen Zaidel-Bar, Alexander D Bershadsky
Although myosin II filaments are known to exist in non-muscle cells, their dynamics and organization are incompletely understood. Here, we combined structured illumination microscopy with pharmacological and genetic perturbations, to study the process of actomyosin cytoskeleton self-organization into arcs and stress fibres. A striking feature of the myosin II filament organization was their 'registered' alignment into stacks, spanning up to several micrometres in the direction orthogonal to the parallel actin bundles...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28092655/circadian-and-upr-dependent-control-of-cpeb4-mediates-a-translational-response-to-counteract-hepatic-steatosis-under-er-stress
#13
Carlos Maillo, Judit Martín, David Sebastián, Maribel Hernández-Alvarez, Mar García-Rocha, Oscar Reina, Antonio Zorzano, Mercedes Fernandez, Raúl Méndez
The cytoplasmic polyadenylation element-binding (CPEB) proteins regulate pre-mRNA processing and translation of CPE-containing mRNAs in early embryonic development and synaptic activity. However, specific functions in adult organisms are poorly understood. Here we show that CPEB4 is required for adaptation to high-fat-diet- and ageing-induced endoplasmic reticulum (ER) stress, and subsequent hepatosteatosis. Stress-activated liver CPEB4 expression is dual-mode regulated. First, Cpeb4 mRNA transcription is controlled by the circadian clock, and then its translation is regulated by the unfolded protein response (UPR) through upstream open reading frames within the 5'UTR...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28139654/cpeb4-links-the-clock-and-the-upr-to-protect-the-liver
#14
Paul C Moore, Scott A Oakes
Under misfolded protein stress, the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) to restore homeostasis, or commits the cell to apoptosis. A study now uncovers how the UPR is governed by the circadian clock to adjust ER protein-folding capacity to metabolic demand and protect against liver damage.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28139653/corrigendum-mitotic-internalization-of-planar-cell-polarity-proteins-preserves-tissue-polarity
#15
Danelle Devenport, Daniel Oristian, Evan Heller, Elaine Fuchs
No abstract text is available yet for this article.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28139652/lnc-ing-ror1-her3-and-hippo-signalling-in-metastasis
#16
Wei Zhuo, Yibin Kang
Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in cancer progression. The previously uncharacterized lncRNA MAYA is now shown to promote bone metastasis by bridging ROR1-HER3 and Hippo-YAP pathways. Neuregulin-induced HER3 phosphorylation by ROR1 recruits a MAYA-containing protein complex to methylate Hippo/MST1 and activate YAP target genes that are essential for bone metastasis.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28139651/growing-splitting-and-stacking-myosin-ii-filaments
#17
Margaret A Titus
Spectacular images of the process of myosin II filament formation and organization in migrating cells are unveiled by super-resolution imaging. A combination of short- and long-range interactions with actin filaments is seen to play a critical role in filament partitioning and alignment into contractile actin arcs and stress fibres.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28139650/corrigendum-clonal-fate-mapping-quantifies-the-number-of-haematopoietic-stem-cells-that-arise-during-development
#18
Jonathan Henninger, Buyung Santoso, Stefan Hans, Ellen Durand, Jessica Moore, Christian Mosimann, Michael Brand, David Traver, Leonard Zon
No abstract text is available yet for this article.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27992407/lin28-phosphorylation-by-mapk-erk-couples-signalling-to-the-post-transcriptional-control-of%C3%A2-pluripotency
#19
Kaloyan M Tsanov, Daniel S Pearson, Zhaoting Wu, Areum Han, Robinson Triboulet, Marc T Seligson, John T Powers, Jihan K Osborne, Susan Kane, Steven P Gygi, Richard I Gregory, George Q Daley
Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA biogenesis and direct modulation of mRNA translation. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells, which increases its levels via post-translational stabilization...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27992406/nanoscale-architecture-of-cadherin-based-cell%C3%A2-adhesions
#20
Cristina Bertocchi, Yilin Wang, Andrea Ravasio, Yusuke Hara, Yao Wu, Talgat Sailov, Michelle A Baird, Michael W Davidson, Ronen Zaidel-Bar, Yusuke Toyama, Benoit Ladoux, Rene-Marc Mege, Pakorn Kanchanawong
Multicellularity in animals requires dynamic maintenance of cell-cell contacts. Intercellularly ligated cadherins recruit numerous proteins to form supramolecular complexes that connect with the actin cytoskeleton and support force transmission. However, the molecular organization within such structures remains unknown. Here we mapped protein organization in cadherin-based adhesions by super-resolution microscopy, revealing a multi-compartment nanoscale architecture, with the plasma-membrane-proximal cadherin-catenin compartment segregated from the actin cytoskeletal compartment, bridged by an interface zone containing vinculin...
January 2017: Nature Cell Biology
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