• Cilia/metabolism
• Cilia/genetics
• Animals
• Receptor, Fibroblast Growth Factor, Type 2/metabolism
• Receptor, Fibroblast Growth Factor, Type 2/genetics
• Signal Transduction
• Mice
• Epithelial Cells/metabolism
• Humans
• Receptor, Fibroblast Growth Factor, Type 1/metabolism
• Receptor, Fibroblast Growth Factor, Type 1/genetics

• NW24-08-00364 Agency for Healthcare Research of the Czech Republic
• GA23-07631S Czech Science Foundation
• LX22NPO5102 National Institute for Cancer Research
• European Union
• LUAUS23295 Ministry of Education, Youth and Sports of the Czech Republic
• MUNI/G/1771/2020 Agency of the Masaryk University
• CZ.02.2.69/0.0/0.0/19_073/0016943 IGA MUNI
• Brno City Municipality

• er stress
• ferroptosis
• hk-2 cells
• pdia6
• primary cilia

• Ferroptosis/physiology
• Protein Disulfide-Isomerases/metabolism
• Protein Disulfide-Isomerases/genetics
• Endoplasmic Reticulum Stress/physiology
• Humans
• Cilia/metabolism
• Cell Line
• Kidney/metabolism
• Kidney/pathology
• Epithelial Cells/metabolism

• National Research Foundation of Korea
• Ministry of Science and ICT, South Korea
• Ministry of Trade, Industry and Energy
• Ministry of Education

• acid/base balance
• cell migration
• colon cancer
• pHi regulation
• sodium bicarbonate cotransporter

• Humans
• Sodium-Bicarbonate Symporters/metabolism
• Sodium-Bicarbonate Symporters/genetics
• Cell Movement
• Animals
• Cell Proliferation
• Hydrogen-Ion Concentration
• Caco-2 Cells
• Colon/metabolism
• Colon/pathology
• Enterocytes/metabolism
• Cell Adhesion
• Mice
• Mice, Knockout
• Cell Differentiation
• Mice, Inbred C57BL

• SE460/21-1 Deutsche Forschungsgemeinschaft (DFG)
• SE460/22-1 Deutsche Forschungsgemeinschaft (DFG)

• Cilia/metabolism
• Protein Transport
• Signal Transduction
• Biological Transport
• Cytoplasm

• R01 GM112988 NIGMS NIH HHS
• R35 GM118082 NIGMS NIH HHS

• cell migration
• cell polarity
• cilia
• neural patterning

• Cell Polarity
• Cilia/physiology
• Cyclic GMP
• Interneurons/physiology
• Cell Movement/physiology

• Young Investigator grant Brain and Behavior Research Foundation (Brain & Behavior Research Foundation)
• Post-doctoral Fellowship Fondation Jérôme Lejeune (Jérôme Lejeune Foundation)

• aging
• cell signaling
• cilia
• kidney
• pancreas

• Animals
• Mice
• Cilia/physiology
• Kidney
• Polycystic Kidney Diseases
• Pancreas/physiology
• Aging

• PH144/4-3 Deutsche Forschungsgemeinschaft
• PH144/6-1 Deutsche Forschungsgemeinschaft
• 202019-32 Fundació La Marató de TV3

• HSPA9/mortalin
• Mitochondrial stress
• Neurotoxicity
• Primary cilia
• SH-SY5Y cells

• 2020R1A2C2003523 Ministry of Science and ICT, South Korea
• 2020R1A4A1018280 Ministry of Science and ICT, South Korea
• 2020R1I1A1A01074053 National Institute for International Education

• Cilia
• Ciliopathies
• Signaling

• neuronal migration
• primary cilium

• Cilia/metabolism
• Cell Movement/physiology
• Neurons/metabolism
• Centrosome
• Neurogenesis

The five plasma membrane Na⁺/H⁺ exchanger (NHE) isoforms in the gastrointestinal tract are characterized by distinct cellular localization, tissue distribution, inhibitor sensitivities, and physiological regulation. NHE1 (Slc9a1) is ubiquitously expressed along the gastrointestinal tract in the basolateral membrane of enterocytes, but so far, an exclusive role for NHE1 in enterocyte physiology has remained elusive. NHE2 (Slc9a2) and NHE8 (Slc9a8) are apically expressed isoforms with ubiquitous distribution along the colonic crypt axis. They are involved in pH_i regulation of intestinal epithelial cells. Combined use of a knockout mouse model, intestinal organoid technology, and specific inhibitors revealed previously unrecognized actions of NHE2 and NHE8 in enterocyte proliferation and differentiation. NHE3 (Slc9a3), expressed in the apical membrane of differentiated intestinal epithelial cells, functions as the predominant nutrient-independent Na⁺ absorptive mechanism in the gut. The new selective NHE3 inhibitor (Tenapanor) allowed discovery of novel pathophysiological and drug-targetable NHE3 functions in cystic-fibrosis associated intestinal obstructions. NHE4, expressed in the basolateral membrane of parietal cells, is essential for parietal cell integrity and acid secretory function, through its role in cell volume regulation. This review focuses on the expression, regulation and activity of the five plasma membrane Na⁺/H⁺ exchangers in the gastrointestinal tract, emphasizing their role in maintaining intestinal homeostasis, or their impact on disease pathogenesis. We point to major open questions in identifying NHE interacting partners in central cellular pathways and processes and the necessity of determining their physiological role in a system where their endogenous expression/activity is maintained, such as organoids derived from different parts of the gastrointestinal tract.

• NHE1
• NHE3
• SGLT1
• SGLT2
• cardiovascular diseases
• diabetes
• sodium–glucose cotransporter inhibitors
• sodium–hydrogen exchanger

• Animals
• Cardiovascular Diseases/drug therapy
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/metabolism
• Cardiovascular Diseases/pathology
• Diabetes Mellitus, Type 2/complications
• Diabetic Cardiomyopathies/drug therapy
• Diabetic Cardiomyopathies/etiology
• Diabetic Cardiomyopathies/metabolism
• Diabetic Cardiomyopathies/pathology
• Humans
• Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
• Sodium-Hydrogen Exchangers/metabolism

• cilia
• ciliopathies
• epistasis
• modifier
• oligogenic
• pleiotropy
• signaling

• alveolar development
• emphysema
• myofibroblast
• signaling endosome

• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• Animals
• Endosomes/genetics
• Endosomes/metabolism
• Fibroblasts/cytology
• Fibroblasts/metabolism
• Lung/cytology
• Lung/metabolism
• Mice
• Mice, Knockout
• Neuropilin-1/genetics
• Neuropilin-1/metabolism
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Receptor, Platelet-Derived Growth Factor beta/genetics
• Receptor, Platelet-Derived Growth Factor beta/metabolism
• Signal Transduction

• I01 BX000508 BLRD VA
• U.S. Department of Veterans Affairs (VA)

• Animals
• Carrier Proteins/metabolism
• Carrier Proteins/physiology
• Cell Adhesion/physiology
• Cell Membrane/metabolism
• Cell Movement/physiology
• Cell Polarity/physiology
• Cilia/metabolism
• Endosomes/metabolism
• Female
• Focal Adhesions/metabolism
• Integrin beta1/metabolism
• Integrins/genetics
• Integrins/metabolism
• Keratinocytes/metabolism
• Male
• Mechanotransduction, Cellular/physiology
• Mice
• Mice, Inbred Strains
• Microtubules/metabolism
• Protein Transport
• Wound Healing/physiology

• R00 AR063161 NIAMS NIH HHS
• 4R00AR063161-03 NIAMS NIH HHS

Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

• Fibrosis
• Idiopathic pulmonary fibrosis
• Kinase
• Transforming growth factor beta

To explore the molecular regulatory mechanisms underlying fibroblast differentiation and dysfunction in the development of adolescent idiopathic scoliosis (AIS) in an effort to identify candidate therapeutic targets for AIS.

The GSE110359 dataset, obtained from the bone marrow stromal cells of 12 AIS patients and five healthy controls, was retrieved from the GEO database. The data were preprocessed and differentially expressed genes (DEGs) were identified. KEGG pathway and Gene Ontology (GO)‐Biological Process (BP) enrichment analyses were performed to identify the function of the DEGs. A protein–protein interaction (PPI) and a microRNA‐transcription factor (TF)‐target co‐regulatory network were constructed to identify hub genes in the development of AIS. In addition, hub DEGs were evaluated by quantitative PCR (qPCR) and immunohistochemical staining.

A total of 188 DEGs including 100 up‐regulated and 88 down‐regulated genes were obtained. The up‐regulated DEGs were related to “p53 signaling pathway”, “FoxO signaling pathway”, and “cGMP‐PKG signaling pathway” terms, while the down‐regulated DEGs were significantly enriched in seven terms including “protein processing in endoplasmic reticulum”. The key up‐regulated genes, PRKG1, CCNG2, and KAT2B, and the key down‐regulated genes, MAP2K1 and DUSP6, were identified by the PPI and miRNA‐TF‐Target regulatory network analyses. mRNA expression patterns for PRKG1, DUSP6, and KAT2B were successfully verified by qPCR. In addition, PRKG1 protein levels were found to be elevated during the immunohistochemical analysis.

Increased expression of PRKG1 in AIS patients might be an attractive therapeutic target for AIS. However, further gain or loss‐of‐function studies should be conducted.

• Adolescent idiopathic scoliosis
• Differentially expressed genes
• PRKG1
• cGMP-PKG signaling pathway

Increasing evidence indicates that ion channels and transporters cooperate in regulating different aspects of tumor pathophysiology. In cancer cells, H⁺/HCO₃^- transporters usually invert the transmembrane pH gradient typically observed in non-neoplastic cells, which is thought to contribute to cancer malignancy. To what extent the pH-regulating transporters are functionally linked to K⁺ channels, which are central regulators of cell membrane potential (V_m), is unclear. We thus investigated in colorectal cancer cells the implication of the pH-regulating transporters and K_V11.1 (also known as hERG1) in the pH modifications stimulated by integrin-dependent cell adhesion. Colorectal cancer cell lines (HCT 116 and HT 29) were seeded onto β1 integrin-dependent substrates, collagen I and fibronectin. This led to a transient cytoplasmic alkalinization, which peaked at 90 min of incubation, lasted approximately 180 min, and was inhibited by antibodies blocking the β1 integrin. The effect was sensitive to amiloride (10 µM) and cariporide (5 µM), suggesting that it was mainly caused by the activity of the Na⁺/H⁺ antiporter NHE1. Blocking K_V11.1 with E4031 shows that channel activity contributed to modulate the β1 integrin-dependent pH_i increase. Interestingly, both NHE1 and K_V11.1 modulated the colorectal cancer cell motility triggered by β1 integrin-dependent adhesion. Finally, the β1 integrin subunit, K_V11.1 and NHE1 co-immunoprecipitated in colorectal cancer cells seeded onto Collagen I, suggesting the formation of a macromolecular complex following integrin-mediated adhesion. We conclude that the interaction between K_V11.1, NHE1, and β1 integrin contributes to regulate colorectal cancer intracellular pH in relation to the tumor microenvironment, suggesting novel pharmacological targets to counteract pro-invasive and, hence, pro-metastatic behavior in colorectal cancer.

• Collagen I
• beta 1 integrin subunit
• cariporide
• hERG1
• integrins
• lateral motility

Using a large-scale quantitative mesenchymal stem cells (MSCs) membrane proteomics analysis, we identified a large group of ciliary proteins in the MSCs membrane fraction, which prompted us to examine the cilia, intricate organelles that were originally discovered approximately 100 years ago. Here we characterize their primary structure and function in MSCs. We first characterized the primary cilia on undifferentiated human MSCs by immunostaining and verified these observation with scanning and 3D electronic microscopy. To investigate the function of the primary cilia of the MSCs we induced loss of function by means of siRNA knockdown (targeted to two known ciliary proteins: IFT172 and KIF3A). After either of these two proteins was knocked down by the respective siRNA, the MSCs showed fewer and shortened primary cilia. The MSCs proliferation assays showed increased cell proliferative activity under confluent conditions after the siRNA knockdown of IFT172 or KIF3A; among these MSCs, the proportion in S phase was increased in the IFT172 siRNA knockdown group. The expression of stem cell markers on the MSCs, namely, Oct4, Nanog and Sox2, were downregulated after the siRNA-induced knockdown of IFT172 or KIF3A, and the gene expression upregulation of ectoderm lineage markers was notable. Furthermore, manipulation of the primary cilia-dependent Shh pathway, using the Shh activator SAG (smoothened agonist), upregulated the gene expression of pluripotency markers, including Nanog and Oct4, and transcriptional target genes in the Shh pathway. This study confirms that MSCs have primary cilia and provides evidence that primary cilia-dependent signaling pathways play functional roles in MSCs proliferation and stemness maintenance.

• Cell cycle
• IFT172
• KIF3A
• Mesenchymal stem cells
• Primary cilia
• Proliferation

• acid-base homeostasis
• genes and evolution
• integrated physiology
• mammalian NHEs
• structure-function and regulation

• Huntingtin
• Nuclear pore
• Primary cilium
• Signaling scaffold molecule
• Transmembrane receptor

• 4
• 5-trisphosphate
• endocytosis
• endosome
• lysosome
• nucleus
• phosphatidylinositol-3
• phosphatidylinositol-3-kinase
• plasma membrane
• receptor tyrosine kinase

Ventricular Septal Defect (VSD), the most common congenital heart defect, is characterized by a hole in the septum between the right and left ventricles. The pathogenesis of VSD is unknown in most clinical cases. There is a paucity of data relevant to epigenetic changes in VSD. The placenta is a fetal tissue crucial in cardiac development and a potentially useful surrogate for evaluating the development of heart tissue. To understand epigenetic mechanisms that may play a role in the development of VSD, genome-wide DNA methylation assay on placentas of 8 term subjects with isolated VSD and no known or suspected genetic syndromes and 10 unaffected controls was performed using the Illumina HumanMethylation450 BeadChip assay. We identified a total of 80 highly accurate potential CpGs in 80 genes for detection of VSD; area under the receiver operating characteristic curve (AUC ROC) 1.0 with significant 95% CI (FDR) p-values < 0.05 for each individual locus. The biological processes and functions for many of these differentially methylated genes are previously known to be associated with heart development or disease, including cardiac ventricle development (HEY2, ISL1), heart looping (SRF), cardiac muscle cell differentiation (ACTC1, HEY2), cardiac septum development (ISL1), heart morphogenesis (SRF, HEY2, ISL1, HEYL), Notch signaling pathway (HEY2, HEYL), cardiac chamber development (ISL1), and cardiac muscle tissue development (ACTC1, ISL1). In addition, we identified 8 microRNAs that have the potential to be biomarkers for the detection of VSD including: miR-191, miR-548F1, miR-148A, miR-423, miR-92B, miR-611, miR-2110, and miR-548H4. To our knowledge this is the first report in which placental analysis has been used for determining the pathogenesis of and predicting VSD.

• Case-Control Studies
• CpG Islands
• DNA Methylation/genetics
• Epigenesis, Genetic
• Female
• Fetal Heart/abnormalities
• Fetal Heart/embryology
• Fetal Heart/metabolism
• Genetic Markers
• Heart Septal Defects, Ventricular/embryology
• Heart Septal Defects, Ventricular/etiology
• Heart Septal Defects, Ventricular/genetics
• Humans
• Infant, Newborn
• Male
• MicroRNAs/genetics
• Placenta/metabolism
• Pregnancy

• cancer
• ciliopathy
• obesity
• receptor tyrosine kinases
• ubiquitin‐mediated protein degradation

To establish a functional and molecular model of the intracellular pH (pH_i) regulatory mechanism in human induced pluripotent stem cells (hiPSCs).

hiPSCs (HPS0077) were kindly provided by Dr. Dai from the Tri-Service General Hospital (IRB No. B-106-09). Changes in the pH_i were detected either by microspectrofluorimetry or by a multimode reader with a pH-sensitive fluorescent probe, BCECF, and the fluorescent ratio was calibrated by the high K⁺/nigericin method. NH₄Cl and Na-acetate prepulse techniques were used to induce rapid intracellular acidosis and alkalization, respectively. The buffering power (β) was calculated from the ΔpH_i induced by perfusing different concentrations of (NH₄)₂SO₄. Western blot techniques and immunocytochemistry staining were used to detect the protein expression of pH_i regulators and pluripotency markers.

In this study, our results indicated that (1) the steady-state pH_i value was found to be 7.5 ± 0.01 (n = 20) and 7.68 ± 0.01 (n =20) in HEPES and 5% CO₂/HCO₃^--buffered systems, respectively, which were much greater than that in normal adult cells (7.2); (2) in a CO₂/HCO₃^--buffered system, the values of total intracellular buffering power (β) can be described by the following equation: β_tot = 107.79 (pH_i)² - 1522.2 (pH_i) + 5396.9 (correlation coefficient R² = 0.85), in the estimated pH_i range of 7.1-8.0; (3) the Na⁺/H⁺ exchanger (NHE) and the Na⁺/HCO₃^- cotransporter (NBC) were found to be functionally activated for acid extrusion for pH_i values less than 7.5 and 7.68, respectively; (4) V-ATPase and some other unknown Na⁺-independent acid extruder(s) could only be functionally detected for pH_i values less than 7.1; (5) the Cl^-/ OH^- exchanger (CHE) and the Cl^-/HCO₃^- anion exchanger (AE) were found to be responsible for the weakening of intracellular proton loading; (6) besides the CHE and the AE, a Cl^--independent acid loading mechanism was functionally identified; and (7) in hiPSCs, a strong positive correlation was observed between the loss of pluripotency and the weakening of the intracellular acid extrusion mechanism, which included a decrease in the steady-state pH_i value and diminished the functional activity and protein expression of the NHE and the NBC.

For the first time, we established a functional and molecular model of a pH_i regulatory mechanism and demonstrated its strong positive correlation with hiPSC pluripotency.

• Microspectrofluorimetry
• Human induced pluripotent stem cells
• Na⁺/H⁺ exchanger
• Na⁺/HCO₃^- cotransporter
• Cl^-/OH^- exchanger
• Cl^-/HCO₃^- exchanger
• V-ATPase
• Intracellular buffering power
• Intracellular pH
• BCECF

• EGF
• MDCK cells
• NHE1
• Na+/H+ exchanger
• collective cell migration
• metastasis

The cilium, once considered a vestigial structure, is a conserved, microtubule-based organelle critical for transducing extracellular chemical and mechanical signals that control cell polarity, differentiation, and proliferation. The cilium undergoes cycles of assembly and disassembly that are controlled by complex inter-relationships with the cytoskeleton. Microtubules form the core of the cilium, the axoneme, and are regulated by post-translational modifications, associated proteins, and microtubule dynamics. Although actin and septin cytoskeletons are not major components of the axoneme, they also regulate cilium organization and assembly state. Here, we discuss recent advances on how these different cytoskeletal systems­ affect cilium function, structure, and organization.

• actin
• cilia
• cytoskeleton
• microtubule
• organelle biogenesis
• signaling

• Autophagy
• Hedgehog signaling
• LC3b
• Primary cilia
• TGF-β signaling
• TSC
• WNT5a
• mTOR

• Animals
• Cells, Cultured
• Cilia/metabolism
• Embryo, Mammalian/cytology
• Fibroblasts/metabolism
• Gene Expression Regulation
• Hedgehog Proteins/genetics
• Hedgehog Proteins/metabolism
• Mice, Knockout
• RNA Interference
• Signal Transduction
• Smoothened Receptor/genetics
• Smoothened Receptor/metabolism
• Tuberous Sclerosis Complex 1 Protein
• Tuberous Sclerosis Complex 2 Protein
• Tumor Suppressor Proteins/genetics
• Tumor Suppressor Proteins/metabolism
• Zinc Finger Protein Gli2/genetics
• Zinc Finger Protein Gli2/metabolism

• 12-127196 Sundhed og Sygdom, Det Frie Forskningsråd

• intraflagellar transport
• kinesin-2
• kinesin-3
• primary cilia
• signalling

• Hedgehog
• Migration
• Pdgf
• Primary cilia
• Proliferation
• Wnt

PDGFRα signals from cilia to control development and tumorigenesis. Schmid et al. now show that intraflagellar transport protein 20 (IFT20) interacts with and stabilizes the E3 ubiquitin ligases c-Cbl and Cbl-b to promote feedback inhibition of PDGFRα signaling at the primary cilium.

Primary cilia have pivotal roles as organizers of many different signaling pathways, including platelet-derived growth factor receptor α (PDGFRα) signaling, which, when aberrantly regulated, is associated with developmental disorders, tumorigenesis, and cancer. PDGFRα is up-regulated during ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown. Here, we provide evidence that intraflagellar transport protein 20 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquitination and internalization of PDGFRα for feedback inhibition of receptor signaling. In wild-type cells treated with PDGF-AA, c-Cbl becomes enriched in the cilium, and the receptor is subsequently ubiquitinated and internalized. In contrast, in IFT20-depleted cells, PDGFRα localizes aberrantly to the plasma membrane and is overactivated after ligand stimulation because of destabilization and degradation of c-Cbl and Cbl-b.

• ARMC9
• Joubert syndrome
• basal body
• cilia
• ciliopathy
• primary cilium
• zebrafish

• bicuspid aortic valve
• cardiac development
• extracellular matrix
• primary cilia

• Adaptor Proteins, Signal Transducing/genetics
• Animals
• Cilia/genetics
• Craniofacial Abnormalities/genetics
• Face/abnormalities
• Face/embryology
• Female
• Gene Deletion
• Gene Expression Regulation, Developmental
• Kinesins/genetics
• Male
• Mice
• Neural Crest/embryology
• Neural Crest/metabolism
• Neural Plate/embryology
• Neural Plate/metabolism
• Skull/abnormalities
• Skull/embryology
• Skull/metabolism
• Tumor Suppressor Proteins/genetics

• F31 DE025537 NIDCR NIH HHS
• T32 NS007453 NINDS NIH HHS
• R01 DE023804 NIDCR NIH HHS
• R01 GM112744 NIGMS NIH HHS
• R01 DE019843 NIDCR NIH HHS
• National Institute of Dental and Craniofacial Research
• Foundation for the National Institutes of Health
• National Institute of General Medical Sciences
• March of Dimes Foundation

• Aglossia
• Ciliopathies
• Craniofacial
• Gli
• Mouse
• Neural crest cell
• Primary cilia
• Sonic Hedgehog
• Tongue development

• Autophagy
• Ciliary motility
• Ciliogenesis
• Ciliopathies
• Intraflagellar transport (IFT)
• Nucleoporin
• Primary cilia
• Transition zone

• (P)RR/ATP6AP2
• V-ATPase
• cell cycle
• ciliogenesis
• proliferation

• Cancer
• Metabolism
• Metastasis
• Migration
• Proliferation
• pH

• Animals
• Carcinogenesis/metabolism
• Carcinogenesis/pathology
• Cell Movement
• Cell Survival
• Cellular Reprogramming
• Humans
• Hydrogen-Ion Concentration
• Neoplasms/metabolism
• Neoplasms/pathology

• F32 CA177085 NCI NIH HHS
• R01 CA197855 NCI NIH HHS
• R01 GM116384 NIGMS NIH HHS
• National Institutes of Health

• AURKA
• cilia
• ciliopathy
• human malignancy
• protein–serine–threonine kinases
• signal transduction

• Animals
• Aurora Kinase A/metabolism
• Cilia/enzymology
• Enzyme Activation
• G1 Phase
• Humans
• Mitosis
• Models, Biological
• Neoplasms/enzymology
• Signal Transduction

• P30 CA006927 NCI NIH HHS
• R01 DK108195 NIDDK NIH HHS

• BMP-Smad1/5/8 signaling
• BMPRII
• Osteoblasts
• Primary cilia
• Pulsed electromagnetic fields

• Animals
• Animals, Newborn
• Bone Morphogenetic Protein 2/metabolism
• Bone Morphogenetic Protein Receptors, Type I/metabolism
• Bone Morphogenetic Protein Receptors, Type II/metabolism
• Calcification, Physiologic/drug effects
• Carrier Proteins/pharmacology
• Cell Differentiation/drug effects
• Cilia/metabolism
• Electromagnetic Fields
• Gene Silencing/drug effects
• Humans
• Osteoblasts/cytology
• Osteoblasts/drug effects
• Osteoblasts/metabolism
• Osteogenesis/drug effects
• Pyrazoles/pharmacology
• Pyrimidines/pharmacology
• RNA, Small Interfering/metabolism
• Rats, Wistar
• Signal Transduction/drug effects
• Smad Proteins/metabolism
• Tumor Suppressor Proteins/metabolism
• Up-Regulation/drug effects