J Cancer 2021; 12(24):7349-7357. doi:10.7150/jca.61131 This issue

Research Paper

Downregulation of LOX promotes castration-resistant prostate cancer progression via IGFBP3

Xuanrong Chen1*, Yi Shao1*, Wanqing Wei1,2*, Haishan Shen3*, Yang Li1, Yutong Chen1, Qianwang Ma1, Hanlin Li1, Zhao Yang1, Yuanjie Niu1✉, Zhiqun Shang1✉

1. Department of Urology, Tianjin Institute of Urology, The second hospital of Tianjin Medical University, Tianjin, 300211, China.
2. Department of Pediatric Surgery, Huai'an Maternal and Children Health Hospital, Huai'an 223002, China.
3. Urology Development, Chu Hsien-I Memorial Hospital, Tianjin Medical University, Tianjin, 300211, China.
*These authors contributed equally to this work.

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Chen X, Shao Y, Wei W, Shen H, Li Y, Chen Y, Ma Q, Li H, Yang Z, Niu Y, Shang Z. Downregulation of LOX promotes castration-resistant prostate cancer progression via IGFBP3. J Cancer 2021; 12(24):7349-7357. doi:10.7150/jca.61131. Available from https://www.jcancer.org/v12p7349.htm

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Graphic abstract

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.

Keywords: lysyl oxidase, IGFBP3, castration resistant prostate cancer, progression