PMID- 35717493
OWN - NLM
STAT- MEDLINE
DCOM- 20220621
LR  - 20230119
IS  - 2041-4889 (Electronic)
VI  - 13
IP  - 6
DP  - 2022 Jun 18
TI  - Ct-OATP1B3 promotes high-grade serous ovarian cancer metastasis by regulation of 
      fatty acid beta-oxidation and oxidative phosphorylation.
PG  - 556
LID - 10.1038/s41419-022-05014-1 [doi]
LID - 556
AB  - 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.
CI  - (c) 2022. The Author(s).
FAU - Huang, Yutang
AU  - Huang Y
AD  - Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, 
      China.
FAU - Du, Yan
AU  - Du Y
AD  - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
AD  - Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan 
      University, Shanghai, 200032, China.
FAU - Zheng, Yujie
AU  - Zheng Y
AD  - Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, 
      China.
FAU - Wen, Chunjie
AU  - Wen C
AD  - Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, 
      China.
FAU - Zou, Hecun
AU  - Zou H
AD  - Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, 
      China.
FAU - Huang, Jiafeng
AU  - Huang J
AD  - Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, 
      China.
FAU - Zhou, Honghao
AU  - Zhou H
AD  - Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, 
      China.
AD  - Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central 
      South University, Changsha, 410078, China.
FAU - Zhao, Hongbo
AU  - Zhao H
AUID- ORCID: 0000-0002-7523-9134
AD  - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. 
      zhaohongbo01@sina.com.
AD  - Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan 
      University, Shanghai, 200032, China. zhaohongbo01@sina.com.
AD  - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 
      Shanghai, 200011, China. zhaohongbo01@sina.com.
FAU - Wu, Lanxiang
AU  - Wu L
AUID- ORCID: 0000-0002-6687-2552
AD  - Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, 
      China. lxwu@cqmu.edu.cn.
AD  - Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 
      Chongqing, 400016, China. lxwu@cqmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220618
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Fatty Acids)
RN  - 0 (IGF2BP2 protein, human)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - Fatty Acids
MH  - Female
MH  - Humans
MH  - *Organic Anion Transporters
MH  - *Ovarian Neoplasms/genetics
MH  - Oxidative Phosphorylation
MH  - RNA-Binding Proteins
PMC - PMC9206684
COIS- The authors declare no competing interests.
EDAT- 2022/06/19 06:00
MHDA- 2022/06/22 06:00
PMCR- 2022/06/18
CRDT- 2022/06/18 23:52
PHST- 2021/09/01 00:00 [received]
PHST- 2022/06/09 00:00 [accepted]
PHST- 2022/06/08 00:00 [revised]
PHST- 2022/06/18 23:52 [entrez]
PHST- 2022/06/19 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/06/18 00:00 [pmc-release]
AID - 10.1038/s41419-022-05014-1 [pii]
AID - 5014 [pii]
AID - 10.1038/s41419-022-05014-1 [doi]
PST - epublish
SO  - Cell Death Dis. 2022 Jun 18;13(6):556. doi: 10.1038/s41419-022-05014-1.