Accession |
PRJCA003107 |
Title |
ACSS3/PLIN3 inhibits prostate cancer progression and new endocrine therapy resistance by reducing intratumoral lipid accumulation |
Relevance |
Medical |
Data types |
Transcriptome or Gene expression
|
Organisms |
Homo sapiens
|
Description |
Current endocrine therapy for prostate cancer (PCa) mainly inhibits androgen/androgen receptor (AR) signaling. However, due to increased intratumoural androgen synthesis and AR variation, PCa progresses to castration-resistant prostate cancer (CRPC), which ultimately becomes resistant to new endocrine therapy (NET). A search for new therapeutic perspectives is urgently needed. Here, we found that ACSS3/PLIN3 signaling inhibits PCa progression and reverses NET resistance through reducing the size of intratumoral lipid droplet (LD) deposits. By screening lipid metabolism-related gene sets, we found that ACSS3 was downregulated and predicted a poor prognosis in PCa. Loss of ACSS3 expression was due to gene promoter methylation. Restoration of ACSS3 expression in PCa cells significantly reduced LD deposits, thus promoting apoptosis by increasing endoplasmic reticulum (ER) stress, and decreasing de novo intratumoral androgen synthesis, inhibiting CRPC progression and reversing NET resistance. Mechanistic investigations demonstrated that ACSS3 reduced LD deposits by regulating the stability of the LD coat protein PLIN3. Together, these results establish ACSS3 as a key player and a potential therapeutic target for CRPC. |
Sample scope |
Monoisolate |
Release date |
2020-12-01 |
Publication |
PubMed ID |
Article title |
Journal name |
DOI |
Year |
33391508
|
ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3
|
Theranostics
|
10.7150/thno.49384
|
2021
|
|
Grants |
Agency |
program |
Grant ID |
Grant title |
National Natural Science Foundation of China (NSFC)
|
General Program
|
81672524
|
|
|
Submitter |
Chen
Ke (shenke@hust.edu.cn)
|
Organization |
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology |
Submission date |
2020-07-23 |