title: MCT4 as a potential therapeutic target for metastatic gastric cancer with peritoneal carcinomatosis.
abstract: Monocarboxylate transporters (MCTs) play a major role in up-regulation of glycolysis and adaptation to acidosis. However, the role of MCTs in gastric cancer (GC) is not fully understood. We investigated the potential utilization of a new cancer therapy for GC. We characterized the expression patterns of the MCT isoforms 1, 2, and 4 and investigated the role of MCT in GC through in vitro and in vivo tests using siRNA targeting MCTs. In GC cell lines, MCT1, 2, and 4 were up-regulated with different expression levels; MCT1 and MCT4 were more widely expressed in GC cell lines compared with MCT2. Inhibition of MCTs by siRNA or AR-C155858 reduced cell viability and lactate uptake in GC cell lines. The effect of inhibition of MCTs on tumor growth was also confirmed in xenograft models. Furthermore, MCT inhibition in GC cells increased the sensitivity of cells to radiotherapy or chemotherapy. Compared with normal gastric tissue, no significant alterations of expression levels in tumors were identified for MCT1 and MCT2, whereas a significant increase in MCT4 expression was observed. Most importantly, MCT4 was highly overexpressed in malignant cells of acsites and its silencing resulted in reduced tumor cell proliferation and lactate uptake in malignant ascites. Our study suggests that MCT4 is a clinically relevant target in GC with peritoneal carcinomatosis.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Biological Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: InKyoung
authors.initials: I
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Chang
authors.affiliation: Innovative Cancer Medicine Institute, Samsung Cancer Center, Samsung Medical Center, Seoul, Korea.|Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Su Min
authors.initials: SM
authors.lastname: Ahn
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hae Su
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kwai Han
authors.initials: KH
authors.lastname: Yoo
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ki Sun
authors.initials: KS
authors.lastname: Jung
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Haa-Na
authors.initials: HN
authors.lastname: Song
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Innovative Cancer Medicine Institute, Samsung Cancer Center, Samsung Medical Center, Seoul, Korea.|Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soojin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy / Q000556:secondary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000970:Antineoplastic Agents; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D027981:Symporters; D013876:Thiophenes; D014498:Uracil; D000099233:Monocarboxylate Transport Protein 1; C546977:AR C155858; C406962:SLC16A4 protein, human; C490427:SLC16A7 protein, human
keywords: gastric cancer; glycolysis; monocarboxylate transporter; prognosis