Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 7, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2019.00322
Keywords
ATRA; Pin1; breast cancer; tamoxifen; ER alpha
Categories
Funding
- National Natural Science Foundation of China [81572890, 81772837, 81872370]
- Guangdong Science and Technology Department [2017B030314026]
- Guangdong Natural Science Foundation [2018A0303130322]
- Science and Technology Foundation of the Guangdong Province [2014A050503029, 2019A050510016]
- Sun Yat-sen Initiative Program for Scientific Research [YXQH201701]
- Elite Young Scholar Program of Sun Yat-sen Memorial Hospital [Y201701]
Ask authors/readers for more resources
Breast cancer is the most prevalent tumor in women worldwide and about 70% patients are estrogen receptor positive. In these cancer patients, resistance to the anticancer estrogen receptor antagonist tamoxifen emerges to be a major clinical obstacle. Peptidyl-prolyl isomerase Pin1 is prominently overexpressed in breast cancer and involves in tamoxifen-resistance. Here, we explore the mechanism and effect of targeting Pin1 using its chemical inhibitor all-trans retinoic acid (ATRA) in the treatment of tamoxifen-resistant breast cancer. We found that Pin1 was up-regulated in tamoxifen-resistant human breast cancer cell lines and tumor tissues from relapsed patients. Pin1 overexpression increased the phosphorylation of ER alpha on S118 and stabilized ER alpha protein. ATRA treatment, resembling the effect of Pin1 knockdown, promoted ER alpha degradation in tamoxifen-resistant cells. Moreover, ATRA or Pin1 knockdown decreased the activation of ERK1/2 and AKT pathways. ATRA also reduced the nuclear expression and transcriptional activity of ER alpha. Importantly, ATRA inhibited cell viability and proliferation of tamoxifen-resistant human breast cancer cells in vitro. Slow-releasing ATRA tablets reduced the growth of tamoxifen-resistant human breast cancer xenografts in vivo. In conclusion, ATRA-induced Pin1 ablation inhibits tamoxifen-resistant breast cancer growth by suppressing multifactorial mechanisms of tamoxifen resistance simultaneously, which demonstrates an attractive strategy for treating aggressive and endocrine-resistant tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available