Glutamine depletion regulates Slug to promote EMT and metastasis in pancreatic cancer.

The Journal of Experimental Medicine
Maria Victoria RecouvreuxCosimo Commisso

Abstract

Tumor cells rely on glutamine to fulfill their metabolic demands and sustain proliferation. The elevated consumption of glutamine can lead to intratumoral nutrient depletion, causing metabolic stress that has the potential to impact tumor progression. Here, we show that nutrient stress caused by glutamine deprivation leads to the induction of epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, we demonstrate that glutamine deficiency regulates EMT through the up-regulation of the EMT master regulator Slug, a process that is dependent on both MEK/ERK signaling and ATF4. We find that Slug is required in PDAC cells for glutamine deprivation-induced EMT, cell motility, and nutrient stress survival. Importantly, we decipher that Slug is associated with nutrient stress in PDAC tumors and is required for metastasis. These results delineate a novel role for Slug in the nutrient stress response and provide insight into how nutrient depletion might influence PDAC progression.

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Citations

Aug 20, 2020·The Journal of Experimental Medicine·Rachel H Josselsohn, David A Tuveson
Dec 20, 2020·Cancers·Stephanie AnnettTracy Robson
Mar 5, 2021·Frontiers in Bioengineering and Biotechnology·Hyeon-Yeol ChoJeong-Woo Choi
Mar 21, 2021·Nature Reviews. Gastroenterology & Hepatology·Joel Encarnación-Rosado, Alec C Kimmelman
Jul 17, 2021·European Journal of Pharmacology·Sepideh MirzaeiSaeed Samarghandian
Jun 12, 2021·Frontiers in Oncology·Jinyong FangWenxia Xu
Aug 17, 2021·Frontiers in Oncology·Qing HuaPingbo Xu
Jan 16, 2022·Oncogene·Rana V SmallingOliver G McDonald

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Datasets Mentioned

BETA
GSE150875
GSE71729

Methods Mentioned

BETA
RNA-seq
PCR
Protein Assay

Software Mentioned

Metascape
Infinity capture
Lumenera
GeneGlobe UPX
DEseq2
Prism
GraphPad
GSEA
ImageJ
ImageStudio Lite

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