Evidence map›Paper›PMID 35912727›Full record

ArticleCancer biomarkers : section A of Disease markers2022

Changes in subcellular localization of Lysyl-tRNA synthetase and the 67-kDa laminin receptor in epithelial ovarian cancer metastases.

Dae Hoon Lee, E Sun Paik, Young-Jae Cho, Yoo-Young Lee, Bada Lee, Eui Jin Lee, Jung-Joo Choi, Chel-Hun Choi, Sangmin Lee, Jin Woo Choi and 1 more

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Article in Cancer biomarkers : section A of Disease markers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Dae Hoon LeeDepartment of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, Korea.
E Sun PaikDepartment of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Young-Jae ChoDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yoo-Young LeeDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Bada LeeDepartment of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, Korea.
Eui Jin LeeDepartment of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, Korea.
Jung-Joo ChoiDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chel-Hun ChoiDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sangmin LeeDepartment of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, Korea.
Jin Woo ChoiDepartment of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, Korea.
Jeong-Won LeeDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Samsung Medical Center · KRKyung Hee University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough lysyl-tRNA synthetase (KARS1) is predominantly located in the cytosol, it is also present in the plasma membrane where it stabilizes the 67-kDa laminin receptor (67LR). This physical interaction is strongly increased under metastatic conditions. However, the dynamic interaction of these two proteins and the turnover of KARS1 in the plasma membrane has not previously been investigated.

objectiveOur objective in this study was to identify the membranous location of KARS1 and 67LR and investigate if this changes with the developmental stage of epithelial ovarian cancer (EOC) and treatment with the inhibitor BC-K01. In addition, we evaluated the therapeutic efficacy of BC-K01 in combination with paclitaxel, as the latter is frequently used to treat patients with EOC.

methodsOverall survival and prognostic significance were determined in EOC patients according to KARS1 and 67LR expression levels as determined by immunohistochemistry. Changes in the location and expression of KARS1 and 67LR were investigated in vitro after BC-K01 treatment. The effects of this compound on tumor growth and apoptosis were evaluated both in vitro and in vivo.

resultsEOC patients with high KARS1 and high 67LR expression had lower progression-free survival rates than those with low expression levels of these two markers. BC-K01 reduced cell viability and increased apoptosis in combination with paclitaxel in EOC cell xenograft mouse models. BC-K01 decreased membranous KARS1 expression, causing a reduction in 67LR membrane expression in EOC cell lines. BC-K01 significantly decreased in vivo tumor weight and number of nodules, especially when used in combination with paclitaxel.

conclusionsCo-localization of KARS1 and 67LR in the plasma membrane contributes to EOC progression. Inhibition of the KARS1-67LR interaction by BC-K01 suppresses metastasis in EOC.

Indexed as

Lysine-tRNA LigaseOvarian NeoplasmsAnimalsCarcinoma, Ovarian EpithelialCell Adhesion MoleculesFemaleHumansMicePaclitaxelReceptors, LamininRibosomal ProteinsCell Adhesion MoleculesLysine-tRNA LigasePaclitaxelReceptors, LamininRibosomal Proteinsanticancer agentcancer metastasisLaminin receptorlysyl-tRNA synthetaseprotein-protein interaction

Identifiers

PMID35912727
PMCPMC12364224
OpenAlexW4288043651

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.