Animals

Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy

Dysregulation of extracellular matrix (ECM) deposition and cellular metabolism promotes tumor aggressiveness by sustaining the activity of key growth, invasion, and survival pathways. Yet mechanisms by which biophysical properties of ECM relate to …

[¹⁸F]Fluorocholine and [¹⁸F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM

PURPOSE: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by inactivating mutations of the TSC1 or TSC2 gene, characterized by neurocognitive impairment and benign tumors of the brain, skin, heart, and kidneys. …

Systems Biology Approaches to Redox Metabolism in Stress and Disease States

SIGNIFICANCE: All cellular metabolic processes are tied to the cellular redox environment. Therefore, maintaining redox homeostasis is critically important for normal cell function. Indeed, redox stress contributes to the pathobiology of many human …

GAPDH Inhibits Intracellular Pathways during Starvation for Cellular Energy Homeostasis

Starvation poses a fundamental challenge to cell survival. Whereas the role of autophagy in promoting energy homeostasis in this setting has been extensively characterized(1), other mechanisms are less well understood. Here we reveal that …

NEDD9 Targets COL3A1 to Promote Endothelial Fibrosis and Pulmonary Arterial Hypertension

Germline mutations involving small mothers against decapentaplegic-transforming growth factor-beta (SMAD-TGF-beta) signaling are an important but rare cause of pulmonary arterial hypertension (PAH), which is a disease characterized, in part, by …

P62/SQSTM1 Cooperates with Hyperactive mTORC1 to Regulate Glutathione Production, Maintain Mitochondrial Integrity, and Promote Tumorigenesis

p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autophagic substrate that accumulates in cells with hyperactive mTORC1, such as kidney cells with mutations in the tumor suppressor genes tuberous sclerosis complex (TSC)1 or TSC2. …

Vascular Stiffness Mechanoactivates YAP/TAZ-Dependent Glutaminolysis to Drive Pulmonary Hypertension

Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH …

Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

BACKGROUND: The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension, suggesting that aldosterone may contribute to …