Downregulation of LOX promotes castration-resistant prostate cancer progression via IGFBP3
| Autor: | Xuanrong Chen, Yuanjie Niu, Zhiqun Shang, Qianwang Ma, Zhao Yang, Yang Li, Haishan Shen, Yi Shao, Yutong Chen, Wanqing Wei, Hanlin Li |
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| Rok vydání: | 2021 |
| Předmět: |
castration resistant prostate cancer
endocrine system diseases integumentary system business.industry IGFBP3 food and beverages Castration resistant urologic and male genital diseases medicine.disease enzymes and coenzymes (carbohydrates) Prostate cancer Oncology Downregulation and upregulation Cancer research Medicine progression lysyl oxidase business Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | The role of lysyl oxidase (LOX) in prostate cancer remains controversial. Studies have shown that LOX may inhibit the progression of prostate cancer (PCa), whereas other studies demonstrate that LOX may act as a tumor activator in PCa. Here, we report that low LOX expression contributes to CRPC progression through upregulation of IGFBP3. We showed that LOX expression decreased in the more advanced and aggressive castration-resistant prostate cancer (CRPC), compared to castration-sensitive prostate cancer (CSPC). We demonstrated that LOX was negatively correlated with IGFBP3 and may directly bind to the promoter of IGFBP3 and thus decrease the expression of IGFBP3. Inhibition of IGFBP3 by siRNA suppressed the growth and migration of CRPC cells, suggesting a critical role for IGFBP3 in CRPC. The preclinical study in a mouse model suggested that introducing back LOX inhibited the progression of CRPC. In summary, we identified a new function of LOX in PCa and discovered that LOX downregulation contributed to progression via IGFBP3, and that the restoration of LOX may be a promising therapeutic strategy for PCa. |
| Databáze: | OpenAIRE |
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