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| Status |
Public on Nov 19, 2021 |
| Title |
BCL6 Enables Cancer Cells to Evade Genotoxic Stress |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Genotoxic agents remain the mainstay of cancer treatment. Unfortunately, clinical benefit is often countered by a rapid adaptive response in tumors. Here we report that the proto-oncogene BCL6 is a core component conferring tumor resistance adaption. In response to genotoxic stress, BCL6 transcription was markedly promoted in cancer cells. BCL6 upregulation was positively associated with therapy resistance and poor progression-free survival in patients. Mechanistically, we discovered that treatment of the genotoxic agent etoposide led to transcriptional reprogramming of multiple proinflammatory cytokines, among which interferon-α and interferon-γ response were significantly enriched in resistant cells. Our results further revealed that the interferon/STAT1 axis that was required for the therapeutic efficacy of etoposide directly regulated BCL6 expression. Increased BCL6 consequently activated mTOR pathway through repressing the tumor suppressor PTEN to enable cancer cell survival. Importantly, targeted inhibition of BCL6 potentiated etoposide-triggered DNA damage and apoptosis in vitro and in vivo. Collectively, our findings highlight the significance of targeting previously uncharacterized interferon-mediated BCL6 pathway to conquer tolerance of cancer cells to genotoxic stress.
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| Overall design |
mRNA profiles of Capan2 cells (n = 3) (control, Etoposide 50 µM), H661 cells (n = 3) (control, Etoposide 40 µM), PC9 cells (n = 3) (control, Etoposide 10 µM).
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| Contributor(s) |
Liu Y, Pang X |
| Citation(s) |
35503721 |
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| Submission date |
Nov 19, 2020 |
| Last update date |
May 10, 2022 |
| Contact name |
Yanan Liu |
| E-mail(s) |
Lyn19950902@outlook.com
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| Organization name |
East China Normal University
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| Department |
School of Life Sciences
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| Street address |
500 Dongchuan Road, Minhang District, Shanghai, China
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| City |
China |
| ZIP/Postal code |
200241 |
| Country |
China |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA679550 |
| SRA |
SRP293252 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE161803_Genes-FPKM-expression.txt.txt.gz |
3.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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