Ct-OATP1B3 promotes high-grade serous ovarian cancer metastasis by regulation of fatty acid beta-oxidation and oxidative phosphorylation

作者全名："Huang, Yutang; Du, Yan; Zheng, Yujie; Wen, Chunjie; Zou, Hecun; Huang, Jiafeng; Zhou, Honghao; Zhao, Hongbo; Wu, Lanxiang"

作者地址："[Huang, Yutang; Zheng, Yujie; Wen, Chunjie; Zou, Hecun; Huang, Jiafeng; Zhou, Honghao; Wu, Lanxiang] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Du, Yan; Zhao, Hongbo] Fudan Univ, Obstet & Gynecol Hosp, Shanghai 200011, Peoples R China; [Du, Yan; Zhao, Hongbo] Fudan Univ, Shanghai Med Sch, Dept Obstet & Gynecol, Shanghai 200032, Peoples R China; [Zhou, Honghao] Cent South Univ, Inst Clin Pharmacol, Pharmacogenet Res Inst, Changsha 410078, Peoples R China; [Zhao, Hongbo] Shanghai Key Lab Female Reprod Endocrine Related, Shanghai 200011, Peoples R China; [Wu, Lanxiang] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing 400016, Peoples R China"

通信作者："Wu, LX (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China.; Zhao, HB (通讯作者)，Fudan Univ, Obstet & Gynecol Hosp, Shanghai 200011, Peoples R China.; Zhao, HB (通讯作者)，Fudan Univ, Shanghai Med Sch, Dept Obstet & Gynecol, Shanghai 200032, Peoples R China.; Zhao, HB (通讯作者)，Shanghai Key Lab Female Reprod Endocrine Related, Shanghai 200011, Peoples R China.; Wu, LX (通讯作者)，Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing 400016, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000812682800001

JCR分区：Q1

影响因子：9

年份：2022

卷号：13

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："High-grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy mainly due to its extensive metastasis. Cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3), a newly discovered splice variant of solute carrier organic anion transporter family member 1B3 (SLCO1B3), has been reported to be overexpressed in several types of cancer. However, the biological function of Ct-OATP1B3 remains largely unknown. Here, we reveal that Ct-OATP1B3 is overexpressed in HGSOC and promotes the metastasis of HGSOC in vivo and in vitro. Mechanically, Ct-OATP1B3 directly interacts with insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an RNA-binding protein, which results in enhancement of the mRNA stability and expression of carnitine palmitoyltransferase 1A (CPT1A) and NADH:Ubiquinone Oxidoreductase Subunit A2 (NDUFA2), leading to increased mitochondrial fatty acid beta-oxidation (FAO) and oxidative phosphorylation (OXPHOS) activities. The increased FAO and OXPHOS activities further facilitate adenosine triphosphate (ATP) production and cellular lamellipodia formation, which is the initial step in the processes of tumor cell migration and invasion. Taken together, our study provides an insight into the function and underlying mechanism of Ct-OATP1B3 in HGSOC metastasis, and highlights Ct-OATP1B3 as a novel prognostic marker as well as therapeutic target in HGSOC."

基金机构："Natural Science Foundation of China [82073938, 81971394, 81973119]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0093]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0246]; Open Project Program of Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases [17DZ2273600]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN201900424]; Scientific and Technological Research Program of Yuzhong District, Chongqing [20200102]"

基金资助正文："This work was supported by the Natural Science Foundation of China (No. 82073938, 81971394 and 81973119), Program for Youth Innovation in Future Medicine, Chongqing Medical University (No. W0093), the Natural Science Foundation of Chongqing (No. cstc2020jcyj-msxmX0246), the Open Project Program of Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases (No. 17DZ2273600), Scientific and Technological Research Program of Chongqing Municipal Education Commission (No. KJQN201900424), and Scientific and Technological Research Program of Yuzhong District, Chongqing (No. 20200102)."