Fig 2: Correlation between aortic diameter (mm) and serum tenascin C levels (pg/ml) in patient cohort of AAA (n = 15).

Fig 3: Schematic of how DpC affects the oncogenic signaling pathways involved in pancreatic cancer cell (PC) and pancreatic stellate cell (PSC) bidirectional oncogenic signaling.A, activated PSCs induce ß-catenin and YAP/TAZ signaling in PC cells (see the Legend for Fig. 1A for a full description). B, upon DpC treatment, NDRG1 is upregulated in PC cells. This response inhibits ß-catenin phosphorylation and prevents its entry into the nucleus, where it would normally promote the expression of pro-proliferative proteins (e.g., cyclin D1, c-myc, etc.) and cytokines (e.g., TGF-ß). NDRG1 also inhibits YAP/TAZ entry into the nucleus to prevent its ability to induce proproliferative gene expression. The decreased production of TGF-ß by PC cells prevents their ability to activate adjacent PSCs, which results in a quiescent state, leading to reduced production of TnC and Wnt-3A by these PSCs. This effect further inhibits downstream ß-catenin and YAP/TAZ signaling in PC cells, thereby disrupting cross talk between PC cells and PSCs.

Fig 4: Compression-induced TNC secretion depends on TGF-ß receptor and ERK pathways. TNC secreted by HBE cells at 24 h post-compression, in the presence or absence of U0126 or SB431542. Representative Western blot of three independent experiments shows the detection of basolateral secretion of TNC. Transferrin was detected as a loading control (A). Secreted TNC were detected by ELISA in the basolateral conditioned media (B) and in the apical washes (C) (mean ± SEM, 3 non-asthma donors). **** p < 0.0001, significantly different from vehicle control; $$$$ p < 0.0001, significantly different from vehicle with pressure, analyzed by two-way ANOVA with Bonferroni’s post-hoc test. Each symbol represents each of the three donors. The open symbols represent control condition, and the closed symbols represent compressed condition in non-asthmatic HBE cells (blue symbols; B,C).

Fig 5: NDRG1 attenuates PSC-mediated nuclear localization of YAP/TAZ and ß-catenin in PC cells. NDRG1 expression in (A) PANC-1 cells and (B) MIAPaCa-2 pancreatic cancer (PC) cells decreases both cytoplasmic and nuclear levels of ß-catenin and YAP/TAZ in the presence of pancreatic stellate cell-conditioned medium (PSC CM). Western blot analysis of (A) PANC-1 and (B) MIAPaCa-2 pancreatic cancer cells examining the effect of NDRG1 overexpression versus the vector control (VC) on cytoplasmic and nuclear levels of NDRG1, YAP/TAZ, and ß-catenin after a 24 h incubation in the presence or absence of PSC-conditioned medium (PSC CM). GAPDH and HDAC1 were loading controls for the cytoplasmic and nuclear extracts, respectively. Blots are representative of three independent experiments. Densitometry results are mean ± SD (n = 3). *p < 0.05; **p < 0.01 denote statistical significance comparing NDRG1 overexpression with the respective VC. #p < 0.05 denotes statistical significance comparing PSC CM treatment with control medium alone. C, Western blot analysis of PSCs incubated with either control medium or conditioned medium from MIAPaCa-2 cells (MIAPaCa-2 CM) overexpressing NDRG1 or the VC and then assessed for TnC, YAP/TAZ, p-YAP, ß-catenin, cyclin D1, or a-SMA expression. ß-actin was used as a protein-loading control. Blots are representative of three independent experiments. Densitometry results are mean ± SD (n = 3). *p < 0.05; **p < 0.01 denotes statistical significance comparing NDRG1 CM-treated PSCs with the respective VC CM-treated PSCs. #p < 0.05; ##p < 0.01 denotes statistical significance comparing VC CM treatment with the respective control. D and E, TGF-ß secretion from PANC-1 (D) and MIAPaCa-2 (E) cells into the overlying medium was examined via ELISA after a 24 or 48 h incubation. Results are mean ± SD (n = 3). **p < 0.01; ***p < 0.001 denotes statistical significance comparing NDRG1 overexpressing to the respective VC cells. ##p < 0.01; ###p < 0.001 denote statistical significance comparing the 24 to 48 h time point.