title: eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells.
abstract: Clusterin is a secretory heterodimeric glycoprotein and the overexpression of secretory clusterin (sCLU) promotes cancer cell proliferation and reduces chemosensitivity. Therefore, sCLU might be an effective target for anticancer therapy. In the current study, we identified eIF3f as a novel CLU-interacting protein and demonstrated its novel function as a CLU inhibitor. The overexpression of eIF3f retarded cancer cell growth significantly and induced apoptosis. In addition, eIF3f interacted with the α-chain (1-227) of sCLU. This interaction blocked modification of psCLU, thereby decreasing the expression and secretion of α/β CLU. Consequently, the overexpression of eIF3f suppressed Akt and ERK signaling and subsequently depleted CLU expression. In addition, eIF3F stabilized p53, which increased the expression of p21 and Bax. Interestingly, the expression of Bax was increased without the activation of p53. eIF3f injected into a xenograft model of human cervical cancer in nude mice markedly inhibited tumor growth. The identification of this novel function of eIF3f as a sCLU inhibitor might open novel avenues for developing improved strategies for CLU-targeted anti-cancer therapies.
authors.affiliation: Department of Life Science, YongIn University, Samga-dong Chuingu, Yonginsi, Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Life Science, YongIn University, Samga-dong Chuingu, Yonginsi, Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si Gyeonggi-do, Korea.
authors.forename: Seung Bae
authors.initials: SB
authors.lastname: Rho
authors.affiliation: Department of Life Science, YongIn University, Samga-dong Chuingu, Yonginsi, Korea.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D051152:Clusterin / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection
chemical_list: D051152:Clusterin; C584155:EIF3F protein, human; D039621:Eukaryotic Initiation Factor-3; D034741:RNA, Small Interfering
keywords: apoptosis; cancer; clusterin; eukaryotic translation initiation factor 3; subunit f