Runx1 Role in Epithelial and Cancer Cell Proliferation Implicates Lipid Metabolism and Scd1 and Soat1 Activity
Prachi JainMary NattakomDavid HolowkaDong Hao WangJ. Thomas BrennaAmy T. KuHoang NguyenSherrif F. IbrahimTudorita Tumbar
29
Citation
95
Reference
10
Related Paper
Citation Trend
Abstract:
The role of lipid metabolism in epithelial stem cell (SC) function and carcinogenesis is poorly understood. The transcription factor Runx1 is known to regulate proliferation in mouse epithelial hair follicle (HF) SCs in vivo and in several mouse and human epithelial cancers. We found a novel subset of in vivo Runx1 HFSC target genes related to lipid metabolism and demonstrated changes in distinct classes of lipids driven by Runx1. Inhibition of lipid-enzymes Scd1 and Soat1 activity synergistically reduces proliferation of mouse skin epithelial cells and of human skin and oral squamous cell carcinoma cultured lines. Varying Runx1 levels induces changes in skin monounsaturated fatty acids (e.g., oleate, a product of Scd1) as shown by our lipidome analysis. Furthermore, varying Runx1 levels, the inhibition of Scd1, or the addition of Scd1-product oleate, individually affects the plasma membrane organization (or fluidity) in mouse keratinocytes. These factors also affect the strength of signal transduction through the membranes for Wnt, a pathway that promotes epithelial (cancer) cell proliferation and HFSC activation. Our working model is that HFSC factor Runx1 modulates the fatty acid production, which affects membrane organization, facilitating signal transduction for rapid proliferation of normal and cancer epithelial cells. Stem Cells 2018;36:1603-1616.Objective To investigate the effects of simulated weightlessness on cell proliferation and cell cycle of human gastric carcinoma cell line SGC-7901 and human gastric mucosa cell line HFE-145. Methods A rotating clinostat was used to simulate weightlessness. Every cell line was divided into two groups, one was rotating group, the other was 1G control group. The whole experimental session was 72h. The expressions of PCNA(proliferating cell nuclear antigen) were examined by immunohistochemical stain. The changes of cell cycle were examined by a cytometer. Results Compared with the control group, the cell proliferation of SGC-7901 cell was inhibited in 48h and 72h in the rotating group, and the cell conversion from G1 to S phase was suppressed. Compared with the control group, the cell proliferation of HFE-145 cell was inhibited in 12h in the rotating group, and the cell conversion from G1 to S phase was suppressed. Conclusions the cell proliferation of SGC-7901 cell is inhibited in 48h and 72h during simulated weightlessness by a clinostat, but HFE-145 cells only have present those above-mentioned changes in 12h during simulated weightlessness by a clinostat.
Clinostat
Weightlessness
Cite
Citations (0)
Objective:To study the effected of berberine on cell proliferation,cell cycle and CD44V6 expression in gastric cancer cell(MGC-803).To investigate the mechanism of inhibitory tumor proliferation and tumor metastasis.Methods:MTT assay was used to determine the cell proliferation effected by berberine.The change of cell morphology and cell cycle were detected by laser scanning confocal microscope(LSCM) and flow cytometry,respectively.Immunohistochemical staining and flow cytometry were applied to detect the CD44V6 expression on cell surface.Results:It was found that the proliferation of MCG-803 is inhibited by berberine.The inhibitory rate of drug(10、20、40 μg/ml)is 36 2%、49 7% and 59 3% respectively in a dose-dependent manner.The cell nuclear condensation and formation of apoptotic bodies were found under LSCM.The cell cycle were arrested in G0-G1.The expression of CD44V6 on cell surface was obviously decreased.Conclusion:Berberine could inhibit proliferation of MGC-03 by inducing apoptosis and arresting cell in G0-G1.Berberine could inhibit tumor metastasis by decreasing the expression of CD44V6 on MCG-803.
MTT assay
Cite
Citations (1)
Objective: To observe the effects of total saponins and total polysaccharides extracted from shenmai on the proliferation and migration of vascularendothelial cell.Methods: The effects of total saponins and total polysaccharides from shenmai on the proliferation of ECV-304 cell and gastric carcinoma SGC-7901 as well as ECV-304 cell induced by SGC-7901 cell were measured by MTT colorimetric assay.Their effects on the migration of ECV-304 cell were investigated by agaros assay.Results: When the concentration of total polysaccharides from shenmai was in the range of 0.18～2.88mg/mL,there was no influence on the proliferation of ECV-304 cell and gastric carcinoma SGC-7901 as well as ECV-304 cell induced by SGC-7901 cell when the concentration of total saponins from shenmai was in the range of 0.05～0.8mg/mL,there was no influence on the proliferation of(SGC-)7901 cell,but they were able to inhibit the proliferation of ECV-304 cell and ECV-304 cell induced by SGC-7901 cell.The inhibition was(13.16)%～62.77%.There was no influence of total polysaccharides from shenmai on the migration of ECV-304 cell,but total saponins from shenmai can inhibit the migration of ECV-304 cell.The inhibition was 42%～80%.The compounds of total saponins and total asragalans from shenmai can also inhibit the proliferation and migration of vascularendothelial cell,there were no difference between the compounds and total polysaccharides in statistics.Conclusion:Total saponins from shenmai can inhibit the proliferation of vascularendothelial cell and vascularendothelial cell induced by conditional cultured medium of gastric carcinoma cell,they also can inhibit the migration of vascularendothelial cell.Total saponins from shenmai are active compounds.
Cite
Citations (0)
Abstract There is no cell proliferation in very sparcely plated chick embryo cell cultures. Substituting conditioned medium or adding of ethanol‐fixed homologous cells to the cultures accelerates cell colony growth. The mechanism for the mitogenic action of fixed cells is considered to be the contact stimulation of cell proliferation, and addition of extra cells to sparse culture is believed to mimic the cell micro‐environment existing in subconfluent cultures. The role of diverse cell—cell contacts in cultured cell growth regulation is discussed. The procedure used (addition of ethanol‐fixed cells) may improve normal cell cloning techniques.
Cloning (programming)
Cite
Citations (1)
Summary: Determinate growth of leaves means that the number and size of their constituent cells must be preciselycontrolled in order to develop to a reproducible size. In the past few years, many mutants and genes involved in the control of cell proliferation and cell expansion in leaves have been identified. In addition, several mutants show an intriguing phenomenon, known as compensated cell enlargement where the reduced number of leaf cells triggers excess cell expansion in leaves. This phenomenon suggests that there is a regulatory system that coordinate cell proliferation and cell expansion. In this review we summarize current knowledge concerning the regulation of cell proliferation and cell expansion and discuss possible mechanisms for compensated cell enlargement. Arabidopsis thaliana, Cell expansion, Cell proliferation, Compensated cell enlargement
Apical cell
Cite
Citations (0)
Abstract Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is an aggressive head and neck malignancy. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play important roles in diverse biological cell processes, such as cell development, fate decisions, cell differentiation, cell migration, and invasion. In our study, we showed that long noncoding RNA colorectal neoplasia differentially expressed (CRNDE) expression was upregulated in TSCC cell lines and tissues. Overexpression of CRNDE increased the TSCC cell proliferation, cell cycle, and cell invasion. Moreover, ectopic expression of CRNDE inhibited the miR‐384 expression in the SCC1 cell and increased the Kirsten Ras (KRAS), cell division cycle 42, and insulin receptor substrate 1 expression, which were the direct target genes of miR‐384. We demonstrated that the miR‐384 expression was downregulated in the TSCC samples compared with the paired adjacent nontumor samples. The expression of CRNDE was negatively correlated with the expression of miR‐384 in the TSCC samples. Overexpression of miR‐384 suppressed TSCC cell proliferation, cell cycle, and invasion. Furthermore, we demonstrated that CRNDE promoted TSCC cell proliferation and invasion through inhibiting miR‐384 expression. These results suggested that CRNDE acts as an oncogene in the development of TSCC, which partially occurs through inhibiting miR‐384 expression.
Ectopic expression
Cite
Citations (21)
In silico characterization of cell–cell interactions using a cellular automata model of cell culture
Cell proliferation is a key characteristic of eukaryotic cells. During cell proliferation, cells interact with each other. In this study, we developed a cellular automata model to estimate cell–cell interactions using experimentally obtained images of cultured cells. We used four types of cells; HeLa cells, human osteosarcoma (HOS) cells, rat mesenchymal stem cells (MSCs), and rat smooth muscle A7r5 cells. These cells were cultured and stained daily. The obtained cell images were binarized and clipped into squares containing about 104 cells. These cells showed characteristic cell proliferation patterns. The growth curves of these cells were generated from the cell proliferation images and we determined the doubling time of these cells from the growth curves. We developed a simple cellular automata system with an easily accessible graphical user interface. This system has five variable parameters, namely, initial cell number, doubling time, motility, cell–cell adhesion, and cell–cell contact inhibition (of proliferation). Within these parameters, we obtained initial cell numbers and doubling times experimentally. We set the motility at a constant value because the effect of the parameter for our simulation was restricted. Therefore, we simulated cell proliferation behavior with cell–cell adhesion and cell–cell contact inhibition as variables. By comparing growth curves and proliferation cell images, we succeeded in determining the cell–cell interaction properties of each cell. Simulated HeLa and HOS cells exhibited low cell–cell adhesion and weak cell–cell contact inhibition. Simulated MSCs exhibited high cell–cell adhesion and positive cell–cell contact inhibition. Simulated A7r5 cells exhibited low cell–cell adhesion and strong cell–cell contact inhibition. These simulated results correlated with the experimental growth curves and proliferation images. Our simulation approach is an easy method for evaluating the cell–cell interaction properties of cells.
Contact inhibition
Cell–cell interaction
HeLa
Cite
Citations (1)
microRNAs (miRNAs) dysregulation is widely involved in cancer progression and contributed to sustained cell proliferation by directly targeting multiple targets. Therefore, better understanding the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In our study, we found that mir-765 is upregulated in both hepatocellular carcinoma (HCC) cell lines and tissues, compared to human normal liver cell line and adjacent non-cancerous tissues, respectively. Overexpression of mir-765 increased HCC cells proliferation and tumorigenicity, whereas inhibition of mir-765 reverses this effect. Furthermore, we demonstrated that INPP4B as a direct target of mir-765 and ectopic expression of mir-765 repressed INPP4B expression, resulting in upregulation of p-AKT, Cyclin D1, and downregulation of p-FOXO3a, p21 expression in HCC. Strikingly, we found that silencing the expression of INPP4B is the essential biological function of miR-765 during HCC cell proliferation. Collectively, our findings reveal that miR-765 is a potential onco-miR that participates in carcinogenesis of human HCC by suppressing INPP4B expression, and might represent a potential therapeutic target for HCC patients.
Ectopic expression
Cyclin E1
Cite
Citations (59)
We report a novel mechanism of cellular growth control. Increasing the density of endothelial or smooth muscle cells in culture increased cell‐cell contact and decreased cell spreading, leading to growth arrest. Using a new method to independently control cell‐cell contact and cell spreading, we found that introducing cell‐cell contact positively regulates proliferation, but that contact‐mediated proliferation can be masked by changes in cell spreading: Round cells with many contacts proliferated less than spread cells with none. Physically blocking cell‐cell contact or inhibiting PI3K signaling abrogated cell‐cell induced proliferation, but inhibiting diffusible paracrine signaling did not. Thus, direct cell‐cell contact induces proliferation in these cells.
Contact inhibition
Cell Signaling
Cite
Citations (259)
Objective To investigate the suppressive effect of Resverol(Res) on proliferation of C6 cell. Methods Res at various concentrations were used to process the C6 cell; the inhibitory action on the growth of C6 cell was evaluated through MTT assay. The cell cycle distribution change and apoptosis induced by Res were examined through flow cytometer (FCM). In addition, the electron microscope was applied to observe the change of the cell's ultra microstructure. Results The experiment showed that Res could suppress the growth and multiplication of C6 cell in a doesand time-dependent manner. Simultaneously Res could effect the C6 cell's cycle distribution, block the cell advancing from G1 to S period. In the experiment the C6 cell apoptosis was induced by Res and the ultra microstructure of C6 cell changed. Conclusion Res obviously suppressed the proliferation of C6 cell and induced its apoptosis and change the cell cycle.
Cite
Citations (0)