Abstract：
:We uncovered a crucial role for the Aurora kinase A (AURKA)-Twist1 axis in promoting epithelial-to-mesenchymal transition (EMT) and chemoresistance in pancreatic cancer. Twist1 is the first EMT-specific target of AURKA that was identified using an innovative screen. AURKA phosphorylates Twist1 at three sites, which results in its multifaceted regulation - AURKA inhibits its ubiquitylation, increases its transcriptional activity and favors its homodimerization. Twist1 reciprocates and prevents AURKA degradation, thereby triggering a feedback loop. Ablation of either AURKA or Twist1 completely inhibits EMT, highlighting both proteins as central players in EMT progression. Phosphorylation-dead Twist1 serves as a dominant-negative and fully reverses the EMT phenotype induced by Twist1, underscoring the crucial role of AURKA-mediated phosphorylation in mediating Twist1-induced malignancy. Likewise, Twist1-overexpressing BxPC3 cells formed large tumors in vivo, whereas expression of phosphorylation-dead Twist1 fully abrogated this effect. Furthermore, immunohistochemical analysis of pancreatic cancer specimens revealed a 3-fold higher level of Twist1 compared to that seen in healthy normal tissues. This is the first study that links Twist1 in a feedback loop with its activating kinase, which indicates that concurrent inhibition of AURKA and Twist1 will be synergistic in inhibiting pancreatic tumorigenesis and metastasis.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Wang J,Nikhil K,Viccaro K,Chang L,Jacobsen M,Sandusky G,Shah Kdoi
10.1242/jcs.196790subject
Has Abstractpub_date
2017-03-15 00:00:00pages
1078-1093issue
6eissn
0021-9533issn
1477-9137pii
jcs.196790journal_volume
130pub_type
杂志文章abstract：:The Sar1 GTPase controls coat assembly on coat protein complex II (COPII)-coated vesicles, which mediate protein transport from the endoplasmic reticulum (ER) to the Golgi. The GTP-bound form of Sar1, activated by the ER-localized guanine nucleotide exchange factor (GEF) Sec12, associates with the ER membrane. GTP hyd...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.189423
更新日期：2016-09-01 00:00:00
abstract：:The atomic force microscope (AFM) was used to directly image hippocampal neurons and glia. Using chemically fixed and living cells it was possible to reconstruct three-dimensional cell structure and detect sub-cellular features such as the nucleus, mitochondria and filaments. By repeatedly scanning a single living cel...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:When expressed in pituitary AtT-20 cells, parotid proline-rich proteins enter the regulated pathway. Because the short N-terminal domain of a basic proline-rich protein is necessary for efficient export from the ER, it has not been possible to evaluate the role of this polypeptide segment as a sorting signal for regul...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:Neurite outgrowth is known as a slow (days) process occurring in nerve cells and neurons during neurotrophin treatment and upon transfer to culture, respectively. Using Y27632, a drug that induces activation of Rac1, a downstream step of the neurotrophin signaling cascade, we have identified a new form of outgrowth, w...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.059634
更新日期：2010-01-15 00:00:00
abstract：:Using finite aperture theory we have shown that localized very dark areas in the interference reflection images of Dictyostelium discoideum amoebae are due to the close intracellular approach of vesicles and tubular elements of the contractile vacuole system to the plasma membrane adjacent to the substratum. Vesicles ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1982-04-01 00:00:00
abstract：:DNA replication in eukaryotic cells initiates from multiple replication origins that are distributed throughout the genome. Coordinating the usage of these origins is crucial to ensure complete and timely replication of the entire genome precisely once in each cell cycle. Replication origins fire according to a cell-t...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.096701
更新日期：2013-03-15 00:00:00
abstract：:Muscle regulatory factors activate myogenesis in all vertebrates, but their role has been studied in great detail only in the mouse embryo, where all but myogenin--Myod, Myf5 and Mrf4--are sufficient to activate (albeit not completely) skeletal myogenesis. In the zebrafish embryo, myod and myf5 are required for induct...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.038356
更新日期：2009-02-15 00:00:00
abstract：:FAS associated factor 1 (FAF1) has been described as an unusual protein that binds to the intracellular portion of the apoptosis signal transducing receptor FAS/Apo-1 and potentiates apoptosis in L-cells. By means of mRNA differential display we have identified the avian homologue (qFAF) as a fibroblast growth factor-...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:The mitotic spindle has long been recognized to play an essential role in determining the position of the cleavage furrow during cell division, however little is known about the mechanisms involved in this process. One attractive hypothesis is that signals from the spindle may function to induce reorganization of cort...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:Developing oral organelles of dividing Tetrahymena corlissi appear to be positioned by mechanisms which assess distances as a proportion of the organism's overall dimensions. In some respects, the cortex of this protozoan obeys the 'French flag' rule formulated by Wolpert for describing regulation of spatial proportio...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-06-01 00:00:00
abstract：:This study focuses on the effect of static and dynamic mechanical compression on the biosynthetic activity of chondrocytes cultured within agarose gel. Chondrocyte/agarose disks (3 mm diameter) were placed between impermeable platens and subjected to uniaxial unconfined compression at various times in culture (2-43 da...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:Human peripheral blood eosinophils attach to and flatten down onto antibody-coated surfaces and subsequently degranulate. An antibody-coated surface was prepared by treating a layer of agar, containing tetanus toxoid antigen and eosinophil chemotactic factor (ECF), with human anti-tetanus immunoglobin. Changes in eosi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1982-08-01 00:00:00
abstract：:Interactions between melanocytes and neighboring cells in the skin are important in regulating skin color in humans. We recently demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates W...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.064774
更新日期：2010-09-15 00:00:00
abstract：:The constitutive recirculation of lymphocytes between the widely distributed organs of the immune system is essential for host defence. We have developed an in vitro model of lymphocyte migration from the blood into lymph nodes which employs primary cultures of high endothelial cells (HEC). HEC-adherent lymphocytes ad...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NFkappaB activation to terminate the signal. We now show that 14-3-3 proteins regulate the NFkappaB signaling pathway by physically interacting with p65 and Ik...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03086
更新日期：2006-09-01 00:00:00
abstract：:Microtubule-associated protein 2 (MAP2) is an abundant neuron-specific protein that binds to microtubules through a domain near its carboxyl terminus that contains either three or four similar repeats of a 31 amino acid motif. When expressed in non-neuronal cells by transfection MAP2 stabilises microtubules and induce...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Interaction of the Eph family of receptor protein tyrosine kinases and their ligands, ephrin family members, induces bi-directional signaling via cell-cell contacts. High expression of B-type ephrin is associated with high invasion potential of tumors, however, the mechanism by which ephrin-B promotes cancer cell inva...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.008607
更新日期：2007-07-01 00:00:00
abstract：:If mitotic-arrested, cold-stored HeLa cells are incubated at 37 degrees C a proportion of the population divides by an aberrant process which we have called subdivision by extrusion. This process has been studied by time-lapse photography and shown to differ from normal cleavage in several respects. The cell surface b...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-11-01 00:00:00
abstract：:Endocytosis of caveolae has previously been implicated in the repair of plasma membrane wounds. Here, we show that caveolin-1-deficient fibroblasts lacking caveolae upregulate a tubular endocytic pathway and have a reduced capacity to reseal after permeabilization with pore-forming toxins compared with wild-type cells...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.249524
更新日期：2020-12-01 00:00:00
abstract：:The intraerythrocytic developmental cycle of Plasmodium falciparum is completed with the release of up to 32 invasive daughter cells, the merozoites, into the blood stream. Before release, the final step of merozoite development is the assembly of the cortical pellicle, a multi-layered membrane structure. This unique ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.181230
更新日期：2016-02-15 00:00:00
abstract：:During early stages of meiotic prophase I the nucleus undergoes considerable reorganization, including the clustering of telomeres, the release of contacts between chromosomes and the nuclear membrane, the reorganization of the nucleolus, and chromatin remodeling. Using a light squashing technique for the analysis of ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03155
更新日期：2006-09-15 00:00:00
abstract：:The subcellular localization of human acidic FGF (aFGF; FGF-1) expressed to high levels by using a bacteriophage T7 RNA polymerase-driven vaccinia virus expression system was studied in BHK21 and HeLa cells. Acidic FGF was detected by immunoblotting or immunofluorescence using an affinity-purified rabbit polyclonal an...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：:Centriolar satellites are membrane-less structures that localize and move around the centrosome and cilium complex in a microtubule-dependent manner. They play important roles in centrosome- and cilium-related processes, including protein trafficking to the centrosome and cilium complex, and ciliogenesis, and they are...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.196832
更新日期：2017-04-15 00:00:00
abstract：:Hormone-induced meiotic maturation of the Xenopus oocyte is regulated by complex changes in protein phosphorylation. It is accompanied by a stimulation in the rate of translation, manifest at the level of polypeptide chain initiation. At laser times in the maturation process, this reflects an increased ability for mRN...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:The invasiveness of cells is correlated with the presence of dynamic actin-rich membrane structures called invadopodia, which are membrane protrusions that are associated with localized polymerization of sub-membrane actin filaments. Similar to focal adhesions and podosomes, invadopodia are cell-matrix adhesion sites....
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.052704
更新日期：2009-09-01 00:00:00
abstract：:AMP-activated protein kinase (AMPK), a cellular metabolic sensor, is essential in energy regulation and metabolism. Hepatocyte polarization during liver development and regeneration parallels increased metabolism. The current study investigates the effects of AMPK and its upstream activator LKB1 on polarity and bile c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.068098
更新日期：2010-10-01 00:00:00
abstract：:HSP27 and alphaB-crystallin are both members of the small heat shock protein family. alphaB-crystalllin has been proposed to modulate intermediate filaments and recently a mutation in alphaB-crystallin has been identified as the genetic basis of desmin related myopathy. This disease is characterised in its pathology b...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:To study the influence of the non alpha-helical tail domain of keratins in filament formation, we prepared a truncated keratin 8 mutant, K8/tailless. Using site-directed in vitro mutagenesis we introduced a stop codon in the position coding for amino acid number 417 of the K8/wild-type sequence, thereby deleting 86 am...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:The large GTPase dynamin, long known for its role in endocytosis, has most recently been implicated as a facilitator of cell migration and invasion. Recent observations link dynamin to the cycle of membrane expansion and retraction essential for cell motility. Its role in actin polymerization, membrane deformation and...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.02963
更新日期：2006-05-01 00:00:00
abstract：:The tachyzoite stage of the protozoan parasite Toxoplasma gondii has two populations of microtubules: spindle microtubules and subpellicular microtubules. To determine how these two microtubule populations are regulated, we investigated microtubule behavior during the cell cycle following treatment with microtubule-di...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
