Ct-OATP1B3 promotes high-grade serous ovarian cancer metastasis by regulation of fatty acid beta-oxidation and oxidative phosphorylation.
Ct-OATP1B3 promotes high-grade serous ovarian cancer metastasis by regulation of fatty acid beta-oxidation and oxidative phosphorylation.
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DOI：
10.1038/s41419-022-05014-1
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发表时间：
2022-06-18
影响因子：
9
通讯作者：
Wu, Lanxiang
中科院分区：
文献类型：
--
作者：
Huang, Yutang;Du, Yan;Zheng, Yujie;Wen, Chunjie;Zou, Hecun;Huang, Jiafeng;Zhou, Honghao;Zhao, Hongbo;Wu, Lanxiang
高级别浆液性卵巢癌（HGSOC）是妇科最致命的恶性肿瘤，主要是由于其广泛的转移。癌症型有机阴离子转运多肽1B 3（Ct-OATP 1B 3）是溶质载体有机阴离子转运蛋白家族成员1B 3（SLCO 1B 3）的一种新发现的剪接变异体，在多种癌症中过度表达。然而，Ct-OATP 1B 3的生物学功能在很大程度上仍然未知。在这里，我们揭示了Ct-OATP 1B 3在HGSOC中过表达，并促进HGSOC在体内和体外的转移。在机械上，Ct-OATP 1B 3直接与胰岛素样生长因子2 mRNA结合蛋白2（IGF 2BP 2）（一种RNA结合蛋白）相互作用，导致肉毒碱棕榈酰转移酶1A（CPT 1A）和NADH：泛醌氧化还原酶亚基A2（NDUFA 2）的mRNA稳定性和表达增强，导致线粒体脂肪酸β-氧化（FAO）和氧化磷酸化（OXPHOS）活性增加。FAO和OXPHOS活性的增加进一步促进三磷酸腺苷（ATP）的产生和细胞板状伪足的形成，这是肿瘤细胞迁移和侵袭过程的初始步骤。综上所述，我们的研究提供了对Ct-OATP 1B 3在HGSOC转移中的功能和潜在机制的深入了解，并强调Ct-OATP 1B 3作为HGSOC的新预后标志物以及治疗靶点。
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.
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影响因子：
9.8
作者：
Hoefs, Saskia J. G.;Dieteren, Cindy E. J.;van den Heuvel, Lambert P.
通讯作者：
van den Heuvel, Lambert P.
影响因子：
7.7
作者：
Dai, Ning;Ji, Fei;Avruch, Joseph
通讯作者：
Avruch, Joseph
DOI：
10.1038/nrc4019
发表时间：
2015-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Bowtell DD;Böhm S;Ahmed AA;Aspuria PJ;Bast RC Jr;Beral V;Berek JS;Birrer MJ;Blagden S;Bookman MA;Brenton JD;Chiappinelli KB;Martins FC;Coukos G;Drapkin R;Edmondson R;Fotopoulou C;Gabra H;Galon J;Gourley C;Heong V;Huntsman DG;Iwanicki M;Karlan BY;Kaye A;Lengyel E;Levine DA;Lu KH;McNeish IA;Menon U;Narod SA;Nelson BH;Nephew KP;Pharoah P;Powell DJ Jr;Ramos P;Romero IL;Scott CL;Sood AK;Stronach EA;Balkwill FR
通讯作者：
Balkwill FR
小豆蔻宁通过抑制 HIF-1α 依赖性代谢重编程来抑制乳腺癌生长
DOI：
10.1186/s13046-019-1351-4
发表时间：
2019-08-27
影响因子：
11.3
作者：
Jin, Jinmei;Qiu, Shuiping;Wu, Xiaojun
通讯作者：
Wu, Xiaojun
影响因子：
10.5
作者：
Janiszewska, Michalina;Suva, Mario L.;Stamenkovic, Ivan
通讯作者：
Stamenkovic, Ivan