Abstract
It has been well known that androgen receptor (AR) is critical to prostate cancer development and progression. It has also been documented that AR is expressed in more than 60% of breast tumors, which promotes the growth of estrogen receptor-negative (ER - )/AR-positive (AR + ) breast cancer cells. Thus, AR might be a potential therapeutic target for AR-positive/ER-negative breast cancer patients. Previously we reported that in prostate cancer cells proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14) stabilized AR protein level by removing its ubiquitin chain. In the current study, we studied the USP14-AR protein interaction and cell proliferation status after USP14 reduction or inhibition in breast cancer cells, and our results support the conclusion that targeting USP14 is a novel strategy for treating AR-responsive breast cancer. We found that inhibition of USP14 accelerated the K48-ubiquitination and proteasome-mediated degradation of AR protein. Additionally, both genetic and pharmacological inhibition of USP14 significantly suppressed cell proliferation in AR-responsive breast cancer cells by blocking G 0 /G 1 to S phase transition and inducing apoptosis. Moreover, AR overexpression inhibited USP14 inhibition-induced events, suggesting that AR deubiquitination by USP14 is critical for breast cancer growth and USP14 inhibition is a possible strategy to treat AR-positive breast cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1896-1910 |
| Number of pages | 15 |
| Journal | Oncogene |
| Volume | 37 |
| Issue number | 14 |
| DOIs | |
| State | Published - Apr 1 2018 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
Cite this
Growth arrest and apoptosis induction in androgen receptor-positive human breast cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination. / Liao, Yuning; Xia, Xiaohong; Liu, Ningning; Cai, Jianyu; Guo, Zhiqiang; Li, Yanling; Jiang, Lili; Dou, Q. Ping; Tang, Daolin; Huang, Hongbiao; Liu, Jinbao.
In: Oncogene, Vol. 37, No. 14, 01.04.2018, p. 1896-1910.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Growth arrest and apoptosis induction in androgen receptor-positive human breast cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination
AU - Liao, Yuning
AU - Xia, Xiaohong
AU - Liu, Ningning
AU - Cai, Jianyu
AU - Guo, Zhiqiang
AU - Li, Yanling
AU - Jiang, Lili
AU - Dou, Q. Ping
AU - Tang, Daolin
AU - Huang, Hongbiao
AU - Liu, Jinbao
PY - 2018/4/1
Y1 - 2018/4/1
N2 - It has been well known that androgen receptor (AR) is critical to prostate cancer development and progression. It has also been documented that AR is expressed in more than 60% of breast tumors, which promotes the growth of estrogen receptor-negative (ER - )/AR-positive (AR + ) breast cancer cells. Thus, AR might be a potential therapeutic target for AR-positive/ER-negative breast cancer patients. Previously we reported that in prostate cancer cells proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14) stabilized AR protein level by removing its ubiquitin chain. In the current study, we studied the USP14-AR protein interaction and cell proliferation status after USP14 reduction or inhibition in breast cancer cells, and our results support the conclusion that targeting USP14 is a novel strategy for treating AR-responsive breast cancer. We found that inhibition of USP14 accelerated the K48-ubiquitination and proteasome-mediated degradation of AR protein. Additionally, both genetic and pharmacological inhibition of USP14 significantly suppressed cell proliferation in AR-responsive breast cancer cells by blocking G 0 /G 1 to S phase transition and inducing apoptosis. Moreover, AR overexpression inhibited USP14 inhibition-induced events, suggesting that AR deubiquitination by USP14 is critical for breast cancer growth and USP14 inhibition is a possible strategy to treat AR-positive breast cancer.
AB - It has been well known that androgen receptor (AR) is critical to prostate cancer development and progression. It has also been documented that AR is expressed in more than 60% of breast tumors, which promotes the growth of estrogen receptor-negative (ER - )/AR-positive (AR + ) breast cancer cells. Thus, AR might be a potential therapeutic target for AR-positive/ER-negative breast cancer patients. Previously we reported that in prostate cancer cells proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14) stabilized AR protein level by removing its ubiquitin chain. In the current study, we studied the USP14-AR protein interaction and cell proliferation status after USP14 reduction or inhibition in breast cancer cells, and our results support the conclusion that targeting USP14 is a novel strategy for treating AR-responsive breast cancer. We found that inhibition of USP14 accelerated the K48-ubiquitination and proteasome-mediated degradation of AR protein. Additionally, both genetic and pharmacological inhibition of USP14 significantly suppressed cell proliferation in AR-responsive breast cancer cells by blocking G 0 /G 1 to S phase transition and inducing apoptosis. Moreover, AR overexpression inhibited USP14 inhibition-induced events, suggesting that AR deubiquitination by USP14 is critical for breast cancer growth and USP14 inhibition is a possible strategy to treat AR-positive breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=85040724283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040724283&partnerID=8YFLogxK
U2 - 10.1038/s41388-017-0069-z
DO - 10.1038/s41388-017-0069-z
M3 - Article
C2 - 29353883
AN - SCOPUS:85040724283
VL - 37
SP - 1896
EP - 1910
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 14
ER -