Ovarian Cancer Metastasis

被引：19
作者：
Li, Yichen [1 ,2 ]
Zhang, Qian [6 ]
Wu, Mandi [1 ,2 ]
Zhang, Peidong [6 ]
Huang, Liang [3 ,4 ,5 ]
Ai, Xiaolin [6 ,7 ]
Yang, Zhengnan [3 ,4 ,5 ]
Shen, Qiuhong [3 ,4 ,5 ]
Wang, Yiran [1 ]
Wang, Ping [3 ,4 ,5 ]
Zhou, Shengtao [3 ,4 ,5 ]
He, Ming-Liang [1 ,2 ]
机构：
[1] City Univ Hong Kong, JCC Coll Vet Med & Life Sci, Dept Biomed Sci, Hong Kong, Peoples R China
[2] CityU Shenzhen Res Inst, Shenzhen, Peoples R China
[3] Sichuan Univ, Dept Obstet & Gynecol, Key Lab Birth Defects & Related Dis Women & Child, Chengdu 610041, Sichuan, Peoples R China
[4] Sichuan Univ, State Key Lab Biotherapy, West China Hosp 2, Chengdu 610041, Sichuan, Peoples R China
[5] Collaborat Innovat Ctr, Chengdu 610041, Sichuan, Peoples R China
[6] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China
[7] Sichuan Univ, West China Hosp, Dept Crit Care Med, Chengdu 610041, Sichuan, Peoples R China
来源：
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2022年 / 18卷 / 09期
基金：
中国国家自然科学基金;
关键词：
Ovarian cancer; LncRNA; Golgi complex; Complement C5; MDSC; TUMOR MICROENVIRONMENT; DENDRITIC CELLS; NONCODING RNA; GOLGI; COMPLEMENT; RECEPTOR; KINASE; DIFFERENTIATION; PROGRESSION; FIBRILLIN-1;
D O I：
10.7150/ijbs.70013
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
It is still a big puzzle how ovarian cancer cells and the tumor microenvironment (TME) attract lymphocytes infiltration for facilitating metastasis, a leading cause of death from gynecological malignancies. Using genome-wide LncRNA microarray assay, here we report that a LncRNA associated with ovarian cancer metastasis (LncOVM) is highly correlated with poor prognosis and survival. LncOVM interacts with and stabilizes PPIP5K2 by suppressing ubiquitinated degradation to promote complement C5 secretion from ovarian cancer cells. The TME-enriched complement C5 attracts myeloid-derived suppressor cells (MDSCs) infiltration in TME to facilitate metastasis. Knockdown of LncOVM or PPIP5K2 inhibits tumor progression in xenograft models. Application of C5aR antibody or inhibitor (CCX168) inhibits MDSC recruitment and restores the suppression of tumorigenesis and metastasis in vivo. Our study reveals that suppression of ovarian cancer metastasis can be achieved by targeting MDSC infiltration in TME through disrupting LncOVM-PPIP5K2-complement axis, providing an option for treating ovarian cancer patients.
引用
收藏
页码：3697 / 3713
页数：17
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