Abstract 3900: Β3 adrenergic receptor blockade impairs compensatory mechanism to overcome nutrient deprivation in malignant rhabdoid tumor of the kidney

Abstract

Abstract In this study, the effects of nutrient deprivation in regulating tumor growth and metabolism in Malignant Rhabdoid Tumor of the Kidney (MRTK) was investigated. MRTK is a rare and highly aggressive tumor occurring in infancy and early childhood. Unfortunately, there are not many studies to date that can help us better understand the involvement of metabolism in MRTK growth and progression. However, it is now well known that nutrient deprivation is an environmental stress factor that can influence the behavior of cancer cells leading to reprogramming in metabolism. Here, we first evaluated the effects on cell survival and metabolic adaptation of MRTK G-401 cells after glutamine or tyrosine/phenylalanine deprivation, or both. Then, the involvement of the β3-adrenergic receptor (β3-AR) in regulating the metabolic changes in G-401 cells exposed to limited conditions was investigated. We demonstrated that deprivation of glutamine alone or in combination with tyrosine/phenylalanine enhanced the expression of the glucose transporter GLUT1, associated with increased glucose uptake, ATP production, and oxidative stress, as a compensatory mechanism following amino acid deprivation partially regulated via β3-AR. Indeed, β3-AR antagonism was able to decrease the expression of GLUT1, glucose uptake and survival in G-401 cells. Furthermore, exposure of G-401 cells to limited conditions induced an improved activity of the TCA cycle enzymes leading to a different and enhanced fumarate production. Overall, our results indicate that tyrosine/phenylalanine and glutamine deprivation in MRTK is able to trigger a compensatory mechanism to sustain tumor growth and proliferation. Citation Format: Angela Subbiani, Alessia Boaretto, Daniela Buonvicino, Cecilia Cecchi, Claudio Favre, Maura Calvani. Β3 adrenergic receptor blockade impairs compensatory mechanism to overcome nutrient deprivation in malignant rhabdoid tumor of the kidney [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3900.