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Series GSE62077 Query DataSets for GSE62077
Status Public on Apr 03, 2015
Title RNA-Seq Samples of siTFE3 in 8988T PDA Cell Line to Investigate Transcriptional Control of the Autophagy-Lysosome System
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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
Contributor(s) Perera RM, Bardeesy N, Ross KN
Citation(s) 26168401
Submission date Oct 06, 2014
Last update date May 15, 2019
Contact name Kenneth N Ross
Organization name Dana-Farber Cancer Institute
Department Pediatric Oncology
Street address 450 Brookline Ave., Rm M640
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (6)
GSM1519398 siCTRL rep1
GSM1519399 siCTRL rep2
GSM1519400 siTFE3 construct1 rep1
BioProject PRJNA263163
SRA SRP048669

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Supplementary file Size Download File type/resource
GSE62077_RAW.tar 4.8 Mb (http)(custom) TAR (of FPKM_TRACKING)
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Raw data are available in SRA
Processed data provided as supplementary file

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