Cancers, Vol. 11, Pages 1610: The Epithelial to Mesenchymal Transition Promotes Glutamine Independence by Suppressing GLS2 Expression

Cancers, Vol. 11, Pages 1610: The Epithelial to Mesenchymal Transition Promotes Glutamine Independence by Suppressing GLS2 Expression Cancers doi: 10.3390/cancers11101610 Authors: Esmeralda Ramirez-Peña James Arnold Vinita Shivakumar Robiya Joseph Geraldine Vidhya Vijay Petra den Hollander Neeraja Bhangre Paul Allegakoen Rishika Prasad Zachary Conley José M. Matés Javier Márquez Jeffrey T. Chang Suhas Vasaikar Rama Soundararajan Arun Sreekumar Sendurai A. Mani Identifying bioenergetics that facilitate the epithelial to mesenchymal transition (EMT) in breast cancer cells may uncover targets to treat incurable metastatic disease. Metastasis is the number one cause of cancer-related deaths; therefore, it is urgent to identify new treatment strategies to prevent the initiation of metastasis. To characterize the bioenergetics of EMT, we compared metabolic activities and gene expression in cells induced to differentiate into the mesenchymal state with their epithelial counterparts. We found that levels of GLS2, which encodes a glutaminase, are inversely associated with EMT. GLS2 down-regulation was correlated with reduced mitochondrial activity and glutamine independence even in low-glucose conditions. Restoration of GLS2 expression in GLS2-negative breast cancer cells rescued mitochondrial activity, enhanced glutamine utilization, and inhibited stem-cell properties. Additionally, inhibition of expression of the transcription factor FOXC2...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research