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| Status |
Public on Jan 11, 2021 |
| Title |
m6A alterations through FTO in breast cancer [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Our understanding of posttranscriptional modifications that decorate RNA, a regulatory layer positioned between DNA and proteins, is in its infancy. N6-methyladenosine (m6A) is the most prevalent internal modification in messenger RNAs that is installed and erased by m6A methyltransferases and demethylases. The importance of these enzymes in cancer is rapidly emerging, yet information of their specific mode of actions during disease progression remain largely unknown. In the present study, we report that the m6A RNA demethylase FTO controls EMT and invasion in cancer through regulation of the Wnt pathway. We find that loss of FTO, in contrast to acute myeloid leukemia, is frequent in many cancer types, including breast and prostate cancers. Knockdown of FTO promotes tumor progression – specifically migration and invasion – in breast and prostate cancer cells. Furthermore, implantation of these cells accelerates tumor progression in recipient mice in vivo. In these tumors, FTO depletion leads to m6A-dependent activation of Wnt signaling, which drives an enhanced EMT program and invasion, thus leading to poor clinical outcome. However, loss of FTO also sensitizes cancers cells to Wnt inhibition, offering a rationale for the therapeutic targeting of Wnt for cancer patients with low FTO levels. Together, our work reveals FTO as a novel regulator of EMT and an unexpected mechanism by which Wnt signals are dysregulated in tumors, providing a rationale to stratify cancer patients treated with Wnt inhibitor. These data uncover a previously unrecognized relationship between RNA modification and EMT in cancer.
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| Overall design |
Transcriptome sequencing in RNAi-depleted FTO (5 samples) and control (5 samples) SK-BR-3 cells.
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| Contributor(s) |
Jeschke J, Collignon E, Al Wardi C, Krayem M, Bizet M, Jia Y, Calonne E, Hassabi B, Wimana Z, Morandini R, Deplus R, Putmans P, Dube G, Singh N, Koch A, Shostak K, Rizzotto L, Ross RL, Garaud S, Desmedt C, Bareche Y, Rothe F, Lehmann-Che J, Duterque-Coquillaud M, Leroy X, Menschaert G, Teixeira L, Guo M, Limbach PA, Close P, Chariot A, Leucci E, Ghanem G, Yuan B, Sotiriou C, Marine J, Fuks F |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Mar 20, 2019 |
| Last update date |
Jan 11, 2021 |
| Contact name |
Martin Bizet |
| E-mail(s) |
mbizet@ulb.ac.be
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| Organization name |
Université Libre de Bruxelles
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| Lab |
Cancer Epigenetics
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| Street address |
CP614 route de Lennik 808
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| City |
Bruxelles |
| ZIP/Postal code |
1070 |
| Country |
Belgium |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (10)
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| GSM3680589 |
RNAi FTO SK-BR-3 cell ribodepleted RNAseq repl1 |
| GSM3680590 |
RNAi FTO SK-BR-3 cell ribodepleted RNAseq repl2 |
| GSM3680591 |
RNAi FTO SK-BR-3 cell ribodepleted RNAseq repl3 |
| GSM3680592 |
RNAi FTO SK-BR-3 cell ribodepleted RNAseq repl4 |
| GSM3680593 |
RNAi FTO SK-BR-3 cell ribodepleted RNAseq repl5 |
| GSM3680594 |
RNAi Ctrl SK-BR-3 cell ribodepleted RNAseq repl1 |
| GSM3680595 |
RNAi Ctrl SK-BR-3 cell ribodepleted RNAseq repl2 |
| GSM3680596 |
RNAi Ctrl SK-BR-3 cell ribodepleted RNAseq repl3 |
| GSM3680597 |
RNAi Ctrl SK-BR-3 cell ribodepleted RNAseq repl4 |
| GSM3680598 |
RNAi Ctrl SK-BR-3 cell ribodepleted RNAseq repl5 |
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| This SubSeries is part of SuperSeries: |
| GSE128582 |
m6A alterations through FTO in breast cancer |
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| Relations |
| BioProject |
PRJNA528204 |
| SRA |
SRP188939 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128581_RAW.tar |
3.8 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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