title: HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation.
abstract: Cap-dependent translation has an essential role in the control of cell proliferation by initiating the translation of oncogenes involved in the regulation of cell cycle progression, such as cyclin D1, and its deregulation contributes to the development and progression of various types of cancers. Hematopoietic pre-B-cell leukemia transcription factor interacting protein (HPIP) was found to be overexpressed in gastric cancer (GC) tissues compared to normal tissues and to promote GC growth in vitro and in vivo. However, the mechanism by which HPIP promotes GC cell proliferation remains unknown. In the present study, we found that HPIP activated cap-dependent translation in an AKT/mTORC1 pathway-dependent manner. Blocking cap‑dependent translation with 4EGI-1, a specific eIF4E/eIF4G interaction inhibitor, profoundly abrogated the ability of HPIP to promote G1/S phase transition and GC cell proliferation, while activation of cap-dependent translation by silencing 4E-BP1 expression significantly reversed the inhibitory effect of HPIP knockdown on GC cell proliferation. Furthermore, targeting translation initiation with 4EGI-1 effectively suppre-ssed the ability of HPIP to promote gastric tumor growth in a xenograft mouse model in vivo. All these data indicate that HPIP promotes GC cell proliferation through positive regulation of cap-dependent translation and mproves our understanding of the underlying mechanisms involved in the regulation of GC cell proliferation by HPIP.
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Third Affiliated Hospital, Inner Mongolia Medical University, Baotou, Inner Mongolia 014000, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, The Third Affiliated Hospital, Inner Mongolia Medical University, Baotou, Inner Mongolia 014000, P.R. China.
authors.forename: Shengbin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Affiliated Renmin Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010059, P.R. China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046912:Multiprotein Complexes / Q000378:metabolism; D009368:Neoplasm Transplantation; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C469750:HCFC1R1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D012333:RNA, Messenger; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases