Selective Cytotoxicity of the NAMPT Inhibitor FK866 Toward Gastric Cancer Cells With Markers of the Epithelial-Mesenchymal Transition, Due to Loss of NAPRT

Gastroenterology
Jooyoung LeeHyun Seok Kim

Abstract

Markers of the epithelial-to-mesenchymal transition (EMT) in gastric tumor tissues are associated with poor patient outcomes. We performed a screen to identify pharmacologic compounds that kill gastric cancer cells with EMT-associated gene expression patterns and investigate their mechanisms. We identified 29 gastric cancer cell lines with a gene expression signature previously associated with an EMT subtype, based on data from RNA sequence analyses, and confirmed the mesenchymal phenotypes of 7 lines (Hs746T, SNU1750, MKN1, SK4, SNU484, SNU668, and YCC11), based on invasive activity and protein markers. We screened 1,345 compounds for their ability to kill cells with the EMT signature compared with cell lines without this pattern. We tested the effects of identified compounds in BALB/c nude mice bearing GA077 tumors; mice were given intraperitoneal injections of the compound or vehicle (control) twice daily for 24 days and tumor growth was monitored. Proteins associated with the toxicity of the compounds were overexpressed in MKN1 and SNU484 cells or knocked down in MKN45 and SNU719 using small interfering RNAs. We performed immunohistochemical analyses of 942 gastric cancer tissues and investigated associations between EMT ma...Continue Reading

Citations

May 14, 2019·Journal of Cellular Biochemistry·Jianwei LiJianguo Sun
Sep 9, 2019·Cancer Science·Shamaine Wei Ting Ho, Patrick Tan
Mar 1, 2020·Biomolecules·Alvinsyah Adhityo PramonoJoseph R Bertino
Feb 26, 2019·Yonsei Medical Journal·Yoon Young ChoiWoo Jin Hyung
Oct 11, 2019·Journal of Gastric Cancer·Jaewook Jeon, Jae-Ho Cheong
Jan 5, 2020·Acta Physiologica·Roldan M de GuiaJonas T Treebak
Jun 2, 2020·Frontiers in Pharmacology·Ubaldina GalliAmbra A Grolla
Feb 17, 2019·Archives of Pharmacal Research·Min-Kyue Shin, Jae-Ho Cheong
Jan 12, 2019·Frontiers in Oncology·Keisuke YakuTakashi Nakagawa
Oct 9, 2020·Signal Transduction and Targeted Therapy·Na XieBingwen Zou
Jan 2, 2021·Signal Transduction and Targeted Therapy·Lola E Navas, Amancio Carnero
Apr 25, 2021·Pharmacology & Therapeutics·Gulam Mohmad RatherPhilip Michael Tedeschi
Jun 3, 2021·Nutrients·Moustafa S GhanemAlessio Nencioni
Jul 3, 2021·International Journal of Molecular Sciences·Natasja FranceschiniAnne-Marie Cleton-Jansen

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