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Series GSE139203 Query DataSets for GSE139203
Status Public on Dec 22, 2020
Title A Lysosome independent role for TFEB in activating DNA repair and inhibiting apoptosis in breast cancer cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy with critical roles in several cancers. Lysosomal autophagy promotes cancer survival through degradation of toxic molecules and maintenance of adequate nutrient supply. Doxorubicin (DOX) is the standard of care treatment for triple-negative breast cancer (TNBC); however, chemoresistance at lower doses and toxicity at higher doses limit its usefulness. By targeting pathways of survival, DOX can become an effective antitumor agent. In this study, we examined the role of TFEB in TNBC and its relationship with autophagy and DNA damage induced by DOX. In TNBC cells, TFEB was hypo-phosphorylated and localized to the nucleus upon DOX treatment. TFEB knockdown decreased the viability of TNBC cells while increasing caspase-3 dependent apoptosis. Additionally, inhibition of TFEB-phosphatase calcineurin sensitized cells to DOX-induced apoptosis in a TFEB dependent fashion. Regulation of apoptosis by TFEB was not a consequence of altered lysosomal function, as TFEB continued to protect against apoptosis in the presence of lysosomal inhibitors. RNA-Seq analysis of TFEB knockdown MDA-MB-231 cells identified a significant downregulation in cell cycle and homologous recombination while genes involved in interferon-γ and TNFα signaling were upregulated. In consequence, knockdown of TFEB was found to disrupt DNA repair following DOX, as evidenced by persistent γH2A.X detection. Together, these findings describe in TNBC a novel lysosomal independent function for TFEB in responding to DNA damage.
Overall design MDA-MB-231 cells were transfected with either of two siRNA’s targeting TFEB (n=3 for each siRNA) or a non-targeting control (n=4) and cultured for 48 h before cells were harvested and RNA extracted using the Qiagen RNeasy mini kit according to the manufacturer’s instructions.
Contributor(s) Slade L, Biswas D, Ihionu F, El Hiani Y, Kienesberger PC, Pulinilkunnil T
Citation(s) 31820786, 36372230
Submission date Oct 21, 2019
Last update date Jan 11, 2023
Contact name Thomas Pulinilkunnil
Phone 5066366971
Organization name Dalhousie University
Department Biochemistry and Molecular Biology
Lab Nutrient Signaling Metabolism Laboratory
Street address 100 Tucker park road
City Saint John
State/province New Brunswick
ZIP/Postal code E2L 4L5
Country Canada
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (10)
GSM4133895 MDA_559: siCTRL
GSM4133896 MDA_560: siCTRL
GSM4133897 MDA_561: siCTRL
BioProject PRJNA578739
SRA SRP226507

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Supplementary file Size Download File type/resource
GSE139203_kallisto_txabun_genes_TFEB.txt.gz 1.5 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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