Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases
文献类型：期刊论文
| 作者 | Su, Shang4,9; Cao, Jingchen4; Meng, Xiangqi1,4; Liu, Ruihua4,5,9; Vander Ark, Alexandra4; Woodford, Erica4; Zhang, Reian4,6; Stiver, Isabelle4,6; Zhang, Xiaotun7; Madaj, Zachary B.8 |
| 刊名 | CANCER LETTERS
 |
| 出版日期 | 2022-01-28 |
| 卷号 | 525页码:170-178 |
| ISSN号 | 0304-3835 |
| 关键词 | Enzalutamide resistance Prostate cancer Bone microenvironment TGFBR2 PTH1R |
| DOI | 10.1016/j.canlet.2021.10.042 |
| 通讯作者 | Li, Xiaohong(xiaohong.li@utoledo.edu) |
| 英文摘要 | Enzalutamide resistance has been observed in approximately 50% of patients with prostate cancer (PCa) bone metastases. Therefore, there is an urgent need to investigate the mechanisms and develop strategies to overcome resistance. We observed enzalutamide resistance in bone lesion development induced by PCa cells in mouse models. We found that the bone microenvironment was indispensable for enzalutamide resistance because enzalutamide significantly inhibited the growth of subcutaneous C4-2B tumors and the proliferation of C4-2B cells isolated from the bone lesions, and the resistance was recapitulated only when C4-2B cells were co-cultured with osteoblasts. In revealing how osteoblasts contribute to enzalutamide resistance, we found that enzalutamide decreased TGFBR2 protein expression in osteoblasts, which was supported by clinical data. This decrease was possibly through PTH1R-mediated endocytosis. We showed that PTH1R blockade rescued enzalutamidemediated decrease in TGFBR2 levels and enzalutamide responses in C4-2B cells that were co-cultured with osteoblasts. This is the first study to reveal the contribution of the bone microenvironment to enzalutamide resistance and identify PTH1R as a feasible target to overcome the resistance in PCa bone metastases. |
| WOS关键词 | HORMONE-RELATED PROTEIN ; ANDROGEN RECEPTOR ; STROMAL CELLS ; T-CELLS ; INHIBITOR ; GROWTH ; SURVIVAL ; IDENTIFICATION ; SUPPRESSION ; FIBROBLASTS |
| 资助项目 | National Cancer Institute[R01CA230744] ; Van Andel Institute[53010A] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| 出版者 | ELSEVIER IRELAND LTD |
| WOS记录号 | WOS:000720458900004 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/298997]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Xiaohong |
| 作者单位 | 1.Sun Yat Sen Univ, Affiliated Hosp 6, Guangzhou 510655, Peoples R China 2.Ball Hort Co, West Chicago, IL 60185 USA 3.Michigan State Univ, Coll Human Med, Dept Pediat & Human Dev, Grand Rapids, MI 49503 USA 4.Van Andel Inst, Ctr Canc & Cell Biol, Grand Rapids, MI 49503 USA 5.Inner Mongolia Univ, Hohhot 010021, Peoples R China 6.Univ Michigan, Ann Arbor, MI 48109 USA 7.Mayo Clin, Anat Clin Pathol, Rochester, MN 55905 USA 8.Van Andel Inst, Bioinformat & Biostat Core, Grand Rapids, MI 49503 USA 9.Univ Toledo, Dept Canc Biol, Toledo, OH 43614 USA 10.Harvard Univ, Ctr Math Sci & Applicat, Cambridge, MA 02138 USA |
| 推荐引用方式 GB/T 7714 | Su, Shang,Cao, Jingchen,Meng, Xiangqi,et al. Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases[J]. CANCER LETTERS,2022,525:170-178. |
| APA | Su, Shang.,Cao, Jingchen.,Meng, Xiangqi.,Liu, Ruihua.,Vander Ark, Alexandra.,...&Li, Xiaohong.(2022).Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases.CANCER LETTERS,525,170-178. |
| MLA | Su, Shang,et al."Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases".CANCER LETTERS 525(2022):170-178. |
入库方式： OAI收割
来源：上海药物研究所
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