title: Effect of STAT3 inhibition on the metabolic switch in a highly STAT3-activated lymphoma cell line.
abstract: BACKGROUND
  Signal transducer and activator of transcription (STAT)3 is involved in a metabolic shift in cancer cells, the Warburg effect through its pro-oncogenic activity. To develop efficient STAT3 inhibitors against cancer cells, novel proteomic and metabolic target molecules need to be explored using multi-omics approaches in the context of STAT3 gene inhibition-mediated tumor growth suppression.
  
  
  METHODS
  We found that short hairpin (sh)RNA-mediated STAT3 inhibition suppressed tumor growth in a highly STAT3-activated lymphoma cell line, SCC-3 cells, and we investigated the effect of STAT3 inhibition on metabolic switching using 2-dimensional differential gel electrophoresis and capillary electrophoresis-time of flight-mass spectrometry.
  
  
  RESULTS
  We identified latexin as a proteomic marker candidate and metabolic enzymes including fructose-bisphosphate aldolase A (ALDOA) as a metabolic marker candidate for STAT3-targeting therapy using STAT3-specific shRNA gene transduction. In particular, latexin expression was up-regulated in four STAT3-activated cancer cell lines including SCC-3 transduced with STAT3-specific shRNA. The up-regulation of latexin was identified in SCC-3 tumors transplanted to nude mice after treatment with STAT3 inhibitor.
  
  
  CONCLUSIONS
  Our results suggest that STAT3 inactivation reverses the glycolytic shift by down-regulating key enzymes and that it induces up-regulation of latexin as a tumor-suppressor molecule, which partially results in cancer cell apoptosis and tumor growth suppression.
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Akiyama
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iizuka
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kume
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Komiyama
authors.affiliation: Cancer Diagnostics Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Urakami
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ashizawa
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Omiya
authors.affiliation: Regional Resources Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
authors.affiliation: Office of the President, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D040901:Proteomics; D034622:RNA Interference; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor
keywords: STAT3; Warburg effect; cancer metabolomics; proteomics; shRNA