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SRX723760: GSM1519403: siTFE3 construct2 rep2; Homo sapiens; RNA-Seq
1 ILLUMINA (Illumina HiSeq 2500) run: 31.6M spots, 1.6G bases, 1.1Gb downloads

Submitted by: Gene Expression Omnibus (GEO)
Study: RNA-Seq Samples of siTFE3 in 8988T PDA Cell Line to Investigate Transcriptional Control of the Autophagy-Lysosome System
show Abstracthide Abstract
The activation of cellular quality control pathways to maintain metabolic homeostasis and mitigate diverse cellular stresses is emerging as a critical growth and survival mechanism in many cancers. Autophagy, a highly conserved cellular self-degradative process, is a key player in the initiation and maintenance of pancreatic ductal adenocarcinoma (PDA). However, the regulatory circuits that activate autophagy, and how they enable reprogramming of PDA cell metabolism are unknown. We now show that autophagy regulation in PDA occurs as part of a broader program that coordinates activation of lysosome biogenesis, function and nutrient scavenging, through constitutive activation of the MiT/TFE family of bHLH transcription factors. In PDA cells, the MiT/TFE proteins - MITF, TFE3 and TFEB - override a regulatory mechanism that controls their nuclear translocation, resulting in their constitutive activation. By orchestrating the expression of a coherent network of genes that induce high levels of lysosomal catabolic function, the MiT/TFE factors are required for proliferation and tumorigenicity of PDA cells. Importantly, unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosomal activation is specifically required to maintain intracellular AA pools in PDA. This AA flux is part of a program that is essential for metabolic homeostasis and bioenergetics of PDA but not for their non-transformed counterparts. These results identify the MiT/TFE transcription factors as master regulators of the autophagy-lysosomal system in PDA and demonstrate a central role of the autophagosome-lysosome compartment in maintaining tumor cell metabolism through alternative amino acid acquisition and utilization. Overall design: Examination of mRNA levels in pancreatic ductal adenocarcinoma (PDA) cell line 8988T after treatment with siRNA for control or TFE3
Sample: siTFE3 construct2 rep2
SAMN03097395 • SRS716682 • All experiments • All runs
Organism: Homo sapiens
Library:
Instrument: Illumina HiSeq 2500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: SINGLE
Construction protocol: Illumina TruSeq RNA Sample Prep Kit was used with >1 ug of total RNA for the construction of sequencing libraries. RNA libraries were prepared for sequencing using standard Illumina protocols at the Tufts University Bioinformatics Core (http://tucf-genomics.tufts.edu)
Experiment attributes:
GEO Accession: GSM1519403
Links:
External link:
Runs: 1 run, 31.6M spots, 1.6G bases, 1.1Gb
Run# of Spots# of BasesSizePublished
SRR160140531,593,4301.6G1.1Gb2015-04-03

ID:
1045526

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