Loss of Rb1 Enhances Glycolytic Metabolism in Kras-Driven Lung Tumors In Vivo
CANCERS
Authors: Conroy, Lindsey R.; Dougherty, Susan; Kruer, Traci; Metcalf, Stephanie; Lorkiewicz, Pawel; He, Liqing; Yin, Xinmin; Zhang, Xiang; Arumugam, Sengodagounder; Young, Lyndsay E. A.; Sun, Ramon C.; Clem, Brian F.
Abstract
Dysregulated metabolism is a hallmark of cancer cells and is driven in part by specific genetic alterations in various oncogenes or tumor suppressors. The retinoblastoma protein (pRb) is a tumor suppressor that canonically regulates cell cycle progression; however, recent studies have highlighted a functional role for pRb in controlling cellular metabolism. Here, we report that loss of the gene encoding pRb (Rb1) in a transgenic mutant Kras-driven model of lung cancer results in metabolic reprogramming. Our tracer studies using bolus dosing of [U-C-13]-glucose revealed an increase in glucose carbon incorporation into select glycolytic intermediates. Consistent with this result, Rb1-depleted tumors exhibited increased expression of key glycolytic enzymes. Interestingly, loss of Rb1 did not alter mitochondrial pyruvate oxidation compared to lung tumors with intact Rb1. Additional tracer studies using [U-C-13,N-15]-glutamine and [U-C-13]-lactate demonstrated that loss of Rb1 did not alter glutaminolysis or utilization of circulating lactate within the tricarboxylic acid cycle (TCA) in vivo. Taken together, these data suggest that the loss of Rb1 promotes a glycolytic phenotype, while not altering pyruvate oxidative metabolism or glutamine anaplerosis in Kras-driven lung tumors.
Status of the application of exogenous enzyme technology for the development of natural plant resources
BIOPROCESS AND BIOSYSTEMS ENGINEERING
Authors: Yuan, Bin; Zhou, Shiyu; Liu, Changwei; Zhang, Sheng; Li, Jiayin; Liu, Ailing
Abstract
Exogenous enzymes are extraneous enzymes that are not intrinsic to the subject. The exogenous enzyme industry has been rapidly developing recently. Successful application of recombinant DNA amplification, high-efficiency expression, and immobilization technology to genetically engineered bacteria provides a rich source of enzymes. Amylase, cellulase, protease, pectinase, glycosidase, tannase, and polyphenol oxidase are among the most widely used such enzymes. Currently, the application of exogenous enzyme technology in the development of natural plant resources mainly focuses on improving the taste and flavor of the product, enriching the active ingredient contents, deriving and transforming the structure of a chosen compound, and enhancing the biological activity and utilization of the functional ingredient. In this review, we discuss the application status of exogenous enzyme technology for the development of natural plant resources using typical natural active ingredients from plant, such as resveratrol, steviosides, catechins, mogrosides, and ginsenosides, as examples, to provide basis for further exploitation and utilization of exogenous enzyme technology.