Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells

This article evaluates the effects of enforced overexpression of two known G protein-coupled receptors in two phenotypically distinct breast cancer cell lines

Value of soluble Urokinase plasminogen activator receptor over age as a biomarker of impaired myocardial relaxation

Background: SuPAR is a biomarker that reflects the level of immune activation. As inflammation plays an important role in the ageing process of the cardiovascular system, we hypothesized that suPAR might be a useful predictive biomarker of the ageing heart. Methods: We performed conventional and tissue Doppler echocardiography and measured plasma suPAR levels. Results: We studied community adults (n=120, 37.5% female) (mean age: 70.3±9.3 years) without known cardiovascular disease (CVD). Participants with impaired myocardial relaxation were older (84% vs 59% were aged ≥71 years, p=0.002), with more diabetes mellitus (27% vs 11%, p=0.034). SuPAR levels were higher among participants with impaired myocardial relaxation (3.9 ng/ml vs 3.0 ng/ml, p=0.015). At the univariate level, older age (OR 3.6; 95%CI 1.6, 8.5; p=0.003), diabetes mellitus (OR 3.04; 95%CI 1.1, 8.8; p=0.04), systolic blood pressure (OR 1.03; 95%CI 1.001, 1.1; p=0.041) and suPAR levels ≥3.00ng/ml (OR 3.4; 95%CI 1.16, 7.4; p=0.002) were associated with impaired myocardial relaxation. In multivariable regression analysis, only older age (OR 2.8; 95%CI 1.1, 6.7; p=0.026) and suPAR (OR 2.7; 95%CI 1.2, 6.1; p=0.018) remained independently associated with impaired myocardial relaxation. Receiver operating characteristics (ROC) curve analysis revealed an area under the curve (AUC) value of 0.63 (95% CI 0.54, 0.71) for model that included age alone. Addition of suPAR significantly increased AUC value to 0.70 (95%CI 0.60, 0.79), which was significantly larger than the model with age alone (p=0.016). Conclusion: We demonstrate additional ability of suPAR, over age, to predict impaired myocardial relaxation.ASTAR (Agency for Sci., Tech. and Research, S’pore)NMRC (Natl Medical Research Council, S’pore)Published versio

Anti-invasive phenotype in FFAR2- and FFAR3-overexpressing MDA-MD-231 cells.

<p>(A) MDA-MB-231 cells were seeded in to the upper chambers of Biocoat Matrigel transwells, then treated with vehicle control or with 1 mM propionate for 24 hours. Representative images show cells that have invaded through the matrix. (B) Quantitation of the invasion assay in (A) shows a significant ligand-mediated reduction in the invasiveness in cells overexpressing FFAR2 and FFAR3, but not vector control cells (N = 3). (C) MDA-MB-231 cells were labeled with rhodamine-phalloidin in order to visualize actin filaments. Representative images are shown. (D) Quantification of cells from (C) that demonstrate the presence of stress fibers (N = 3). (*p< 0.05, **p< 0.01).</p

Schematic summarizing the effect of short chain fatty acid receptor overexpression in breast cancer cells.

<p>We provide novel data that demonstrate that activation of FFAR2 can activate LATS1 (repressor of YAP1), which results in an increase in E-cadherin levels. In contrast, FFAR3 activity inhibits the MAP/ERK pathway. These processes are likely to underlie the repressive effect of short chain fatty acid receptors on breast cancer cell invasion.</p

FFAR2 regulates E-cadherin.

<p>(A) qRT-PCR analysis of EMT-related genes was performed on MDA-MB-231 cells overexpressing FFAR2 and FFAR3. Expression of <i>CDH1</i> was selectively increased in FFAR2-overexpressing cells relative to vector controls, while no changes in EMT-related genes were observed in FFAR3-overexpressing cells (N = 3). (B) Cells were treated with vehicle control or with 100 μM propionate for 24 hours, then evaluated for <i>CDH1</i> expression by qRT-PCR. FFAR2-overexpressing cells, but not in vector control cells or in FFAR3-overexpressing cells, demonstrated a ligand-dependent increase in <i>CDH1</i> mRNA (N = 3). (C) Cells were treated with vehicle control or with 100 μM propionate for 24 hours, then evaluated for E-cadherin levels by western blot analysis. Results are representative of three independent experiments. (D) Quantitation of the relative density of the data from (C) demonstrates that E-cadherin is increased in FFAR2-overexpressing cells, and is further increased by propionate treatment (N = 3). (*p< 0.05, **p< 0.01, ***p< 0.001.).</p

Reduced expression of FFAR2 and FFAR3 in invasive and triple negative breast cancer tissues.

<p>The Curtis breast dataset available sourced from Oncomine.org was analyzed for the expression of (A) <i>FFAR2</i> and (B) <i>FFAR3</i> mRNA in 1992 breast carcinoma and 144 normal breast samples. Whiskers represent the minimum to maximum values. One-way ANNOVA was performed to calculate significance. <i>FFAR2</i> expression is reduced in some classes, while <i>FFAR3</i> was reduced in all invasive tumor types. The dataset was analyzed for (C) <i>FFAR2</i> and (D) <i>FFAR3</i> expression level in 144 normal breast tissue samples and in 250 triple negative breast tumors. Expression of both <i>FFAR2</i> and <i>FFAR3</i> were significantly reduced in triple negative breast tumors. (E) Expression data obtained from the Cancer Cell Line Encyclopedia show that among 57 breast cancer cell lines, there is a significant positive correlation between <i>FFAR2</i> and <i>CDH1</i> mRNA levels (Pearson r = 0.516, P <0.001). (F) Expression data obtained from the Human Protein Atlas show that among 1075 primary breast tumor samples, there is a significant positive correlation between <i>FFAR2</i> and <i>CDH1</i> mRNA levels (Pearson r = 0.138, P <0.001).</p

FFAR3 regulates MAP/ERK signaling.

<p>(A) MDA-MB-231 cells were treated with vehicle control or with 1 mM propionate for 24 hours, then evaluated for ERK1/2, pERK1/2, and β-actin levels by western blot analysis. Results are representative of three independent experiments. (B) Quantitation of the relative density of the data from (A) demonstrates that pERK1/2:ERK1/2 ratio is significantly reduced in FFAR3-overexpressing cells, but not in FFAR2-overexpressing cells (N = 3).</p

Large-Scale Highly Aligned Nanowire Printing

Nanowires (NWs) are 1D confined nanostructures; this geometry gives them unique properties that have been exploited in fabrication of high-density and high-tech electronic devices. Current method to produce NWs cannot fabricate large-scale-aligned NW arrays with precise control of length, orientation, location, and number of NWs individually; these inabilities hinder application of NWs in practical electronics. This paper describes e-nanowire printing, a method to print highly aligned NWs on a large scale, and then reviews recent progress in various electronic applications with highly aligned NWs. Finally, future research is suggested to advance nanoelectronics.Y