| RRC ID |
67865
|
| Author |
Takayama KI, Kosaka T, Suzuki T, Hongo H, Oya M, Fujimura T, Suzuki Y, Inoue S.
|
| Title |
Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer.
|
| Journal |
Nat Commun
|
| Abstract |
Interactive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC). Investigation of the transcriptome in castration-resistant PC (CRPC) revealed OCT4 as a key TF in the disease pathology. OCT4 confers epigenetic changes by promoting complex formation with FOXA1 and androgen receptor (AR), the central signals for the progression to CRPC. Meanwhile, OCT4 facilitates a distinctive complex formation with nuclear respiratory factor 1 (NRF1) to gain chemo-resistance in the absence of AR. Mechanistically, we reveal that OCT4 increases large droplet formations with AR/FOXA1 as well as NRF1 in vitro. Disruption of TF collaborations using a nucleoside analogue, ribavirin, inhibited treatment-resistant PC tumor growth. Thus, our findings highlight the formation of TF collaborations as a potent therapeutic target in advanced cancer.
|
| Volume |
12(1)
|
| Pages |
3766
|
| Published |
2021-6-18
|
| DOI |
10.1038/s41467-021-23974-4
|
| PII |
10.1038/s41467-021-23974-4
|
| PMID |
34145268
|
| PMC |
PMC8213733
|
| MeSH |
Animals
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cell Proliferation / genetics
Disease Models, Animal
Drug Resistance, Neoplasm / genetics
Gene Expression Regulation / genetics
Gene Expression Regulation, Neoplastic / genetics
HEK293 Cells
Hepatocyte Nuclear Factor 3-alpha / metabolism*
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Nuclear Respiratory Factor 1 / metabolism
Octamer Transcription Factor-3 / genetics*
Octamer Transcription Factor-3 / metabolism*
Prostatic Neoplasms, Castration-Resistant / genetics*
Prostatic Neoplasms, Castration-Resistant / pathology
Receptors, Androgen / metabolism*
Ribavirin / pharmacology
Signal Transduction
Transcriptome / genetics
|
| IF |
12.121
|
| Resource |
| DNA material |
Venus/pCS2 (RDB15116) |
