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Additional file 3: Supplementary Figure 3.PHGDH knockdown does not affect liver function. shPHGDH (N = 10) and shREN (N = 10) mouse serum was collected and analyzed by IDEXX (Liver Panel). (A) ALP – Alkaline phosphatase. (B) AST – aspartate transaminase. (C) ALT – alanine transaminase. (D) CK – creatine kinase. (E) – Total albumin. (E) Total bilirubin.

Additional file 2: Supplementary Figure 2. shPHGDH mice have poor knockdown in the spleen. Western blot analysis of PHGDH, GFP and HSP90 protein levels in spleen of shPHGDH and shREN mice. Mice were placed on a 200 ppm doxycycline diet for 8 months. ns, non-specific band.

Additional file 4: Supplementary Figure 4.PHGDH knockdown does not affect brain serine and lipids. (A) Brain serine quantities of 5- to 9-month-old shREN (N = 15) and shPHGDH (N = 14) mice. Quantities were normalized to mg of tissue. (B) Quantity of individual ceramides in the brain of 5- to 9-month-old shREN (N = 14) and shPHGDH (N = 15) mice. Quantities were normalized to mg of tissue. (C) Volcano plot of lipidomics analysis of shPHGDH (N = 15) brain compared to shREN (N = 15). Significant metabolites are in bold. Triacylglycerol species are indicated in red. (D) Individual TAG species in the brain of shPHGDH mice compared to shREN. Levels are normalized to shREN.

Additional file 1: Supplementary Figure 1.Validation of shRNAs for model development. NIH3T3 cells expressing Renilla or PHGDH-targeting shRNAs (#1-10) were treated with 1 μg/mL doxycycline for 6 days and PHGDH expression determined by western blot. β-actin is used as a loading control.

Objective: Intra-abdominal fat is a risk factor for pancreatic cancer (PC), but little is known about its contribution to PC precursors known as intraductal papillary mucinous neoplasms (IPMNs). Our goal was to evaluate quantitative radiologic measures of abdominal/visceral obesity as possible diagnostic markers of IPMN severity/pathology.Methods: In a cohort of 34 surgically-resected, pathologically-confirmed IPMNs (17 benign; 17 malignant) with preoperative abdominal computed tomography (CT) images, we calculated body mass index (BMI) and four radiologic measures of obesity: total abdominal fat (TAF) area, visceral fat area (VFA), subcutaneous fat area (SFA), and visceral to subcutaneous fat ratio (V/S). Measures were compared between groups using Wilcoxon two-sample exact tests and other metrics.Results: Mean BMI for individuals with malignant IPMNs (28.9 kg/m2) was higher than mean BMI for those with benign IPMNs (25.8 kg/m2) (P=0.045). Mean VFA was higher for patients with malignant IPMNs (199.3 cm2) compared to benign IPMNs (120.4 cm2), P=0.092. V/S was significantly higher (P=0.013) for patients with malignant versus benign IPMNs (1.25 vs. 0.69 cm2), especially among females. The accuracy, sensitivity, specificity, and positive and negative predictive value of V/S in predicting malignant IPMN pathology were 74%, 71%, 76%, 75%, and 72%, respectively.Conclusions: Preliminary findings suggest measures of visceral fat from routine medical images may help predict IPMN pathology, acting as potential noninvasive diagnostic adjuncts for management and targets for intervention that may be more biologically-relevant than BMI. Further investigation of gender-specific associations in larger, prospective IPMN cohorts is warranted to validate and expand upon these observations.

Using a combination of genomic and metabolomic profiling strategies, the CAMKK2 kinase is identified as a critical downstream target of the androgen receptor. CAMKK2 regulates anabolic flux, and represents an attractive therapeutic target for prostate cancer treatments.

The TIGAR protein has antioxidant activity that supports intestinal tissue repair and adenoma development. Using a pancreatic ductal adenocarcinoma (PDAC) model, we show that reactive oxygen species (ROS) regulation by TIGAR supports premalignant tumor initiation while restricting metastasis. Increased ROS in PDAC cells drives a phenotypic switch that increases migration, invasion, and metastatic capacity. This switch is dependent on increased activation of MAPK signaling and can be reverted by antioxidant treatment. In mouse and human, TIGAR expression is modulated during PDAC development, with higher TIGAR levels in premalignant lesions and lower TIGAR levels in metastasizing tumors. Our study indicates that temporal, dynamic control of ROS underpins full malignant progression and helps to rationalize conflicting reports of pro- and anti-tumor effects of antioxidant treatment.

The TIGAR protein has antioxidant activity that supports intestinal tissue repair and adenoma development. Using a pancreatic ductal adenocarcinoma (PDAC) model, we show that reactive oxygen species (ROS) regulation by TIGAR supports premalignant tumor initiation while restricting metastasis. Increased ROS in PDAC cells drives a phenotypic switch that increases migration, invasion, and metastatic capacity. This switch is dependent on increased activation of MAPK signaling and can be reverted by antioxidant treatment. In mouse and human, TIGAR expression is modulated during PDAC development, with higher TIGAR levels in premalignant lesions and lower TIGAR levels in metastasizing tumors. Our study indicates that temporal, dynamic control of ROS underpins full malignant progression and helps to rationalize conflicting reports of pro- and anti-tumor effects of antioxidant treatment.