PMID- 29254159 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220131 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 60 DP - 2017 Nov 24 TI - Separation of low and high grade colon and rectum carcinoma by eukaryotic translation initiation factors 1, 5 and 6. PG - 101224-101243 LID - 10.18632/oncotarget.20642 [doi] AB - Colorectal cancer (CRC) is the third most common cause of cancer related death worldwide. Furthermore, with more than 1.2 million cases registered per year, it constitutes the third most frequent diagnosed cancer entity worldwide. Deregulation of protein synthesis has received considerable attention as a major step in cancer development and progression. Eukaryotic translation initiation factors (eIFs) are involved in the regulation of protein synthesis and are functionally linked to the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. The identification of factors accounting for colorectal carcinoma (CRC) development is a major gap in the field. Besides the importance of eIF3 subunits and the eIF4 complex, eIF1, eIF5 and eIF6 were found to be altered in primary and metastatic CRC. We observed significant difference in the expression profile between low and high grade CRC. eIF1, eIF5 and eIF6 are involved in translational control in CRC. Our findings also indicate a probable clinical impact when separating them into low and high grade colon and rectum carcinoma. eIF and mTOR expression were analysed on protein and mRNA level in primary low and high grade colon carcinoma (CC) and rectum carcinoma (RC) samples in comparison to non-neoplastic tissue without any disease-related pathology. To assess the therapeutic potential of targeting eIF1, eIF5 and eIF6 siRNA knockdown in HCT116 and HT29 cells was performed. We evaluated the eIF knockdown efficacy on protein and mRNA level and investigated proliferation, apoptosis, invasion, as well as colony forming and polysome associated fractions. These results indicate that eIFs, in particular eIF1, eIF5 and eIF6 play a major role in translational control in colon and rectum cancer. FAU - Golob-Schwarzl, Nicole AU - Golob-Schwarzl N AD - Institute of Pathology, Medical University of Graz, Graz, Austria. AD - Center for Biomarker Research in Medicine, Graz, Austria. FAU - Schweiger, Caroline AU - Schweiger C AD - Institute of Pathology, Medical University of Graz, Graz, Austria. FAU - Koller, Carina AU - Koller C AD - Institute of Pathology, Medical University of Graz, Graz, Austria. FAU - Krassnig, Stefanie AU - Krassnig S AD - Institute of Pathology, Medical University of Graz, Graz, Austria. FAU - Gogg-Kamerer, Margit AU - Gogg-Kamerer M AD - Institute of Pathology, Medical University of Graz, Graz, Austria. FAU - Gantenbein, Nadine AU - Gantenbein N AD - Institute of Pathology, Medical University of Graz, Graz, Austria. AD - Center for Biomarker Research in Medicine, Graz, Austria. FAU - Toeglhofer, Anna M AU - Toeglhofer AM AD - Institute of Pathology, Medical University of Graz, Graz, Austria. FAU - Wodlej, Christina AU - Wodlej C AD - Institute of Pathology, Medical University of Graz, Graz, Austria. AD - Center for Biomarker Research in Medicine, Graz, Austria. FAU - Bergler, Helmut AU - Bergler H AD - Institute of Molecular Biosciences, Karl-Franzens-University of Graz, Graz, Austria. FAU - Pertschy, Brigitte AU - Pertschy B AD - Institute of Molecular Biosciences, Karl-Franzens-University of Graz, Graz, Austria. FAU - Uranitsch, Stefan AU - Uranitsch S AD - Department of Surgery, Hospital Brothers of Charity Graz, Graz, Austria. FAU - Holter, Magdalena AU - Holter M AD - Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria. FAU - El-Heliebi, Amin AU - El-Heliebi A AD - Institute of Cell Biology, Histology and Embryology, Medical University Graz, Graz, Austria. FAU - Fuchs, Julia AU - Fuchs J AD - Institute of Cell Biology, Histology and Embryology, Medical University Graz, Graz, Austria. FAU - Punschart, Andreas AU - Punschart A AD - Department of Surgery, Medical University of Graz, Graz, Austria. FAU - Stiegler, Philipp AU - Stiegler P AD - Department of Surgery, Medical University of Graz, Graz, Austria. FAU - Keil, Marlen AU - Keil M AD - Experimental Pharmacology & Oncology Berlin GmbH-Berlin-Buch, Berlin, Germany. FAU - Hoffmann, Jens AU - Hoffmann J AD - Experimental Pharmacology & Oncology Berlin GmbH-Berlin-Buch, Berlin, Germany. FAU - Henderson, David AU - Henderson D AD - Bayer AG, Berlin, Germany. FAU - Lehrach, Hans AU - Lehrach H AD - Max Planck Institute for Molecular Genetics, Berlin, Germany. FAU - Reinhard, Christoph AU - Reinhard C AD - Eli Lilly & Company, Indianapolis, USA. FAU - Regenbrecht, Christian AU - Regenbrecht C AD - Cpo - cellular phenomics & oncology Berlin-Buch GmbH, Berlin, Germany. FAU - Schicho, Rudolf AU - Schicho R AD - Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria. FAU - Fickert, Peter AU - Fickert P AD - Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria. FAU - Lax, Sigurd AU - Lax S AD - Department of Pathology, Hospital Graz South-West, Austria. FAU - Haybaeck, Johannes AU - Haybaeck J AD - Institute of Pathology, Medical University of Graz, Graz, Austria. AD - Center for Biomarker Research in Medicine, Graz, Austria. AD - Department of Pathology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. LA - eng GR - KLI 521/FWF_/Austrian Science Fund FWF/Austria GR - P 25633/FWF_/Austrian Science Fund FWF/Austria PT - Journal Article DEP - 20170905 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5731869 OTO - NOTNLM OT - PI3K/AKT/mTOR pathway OT - colorectal carcinoma OT - eukaryotic translation initiation factors OT - liver metastases COIS- CONFLICTS OF INTEREST The authors disclose no conflicts of interest. EDAT- 2017/12/20 06:00 MHDA- 2017/12/20 06:01 PMCR- 2017/11/24 CRDT- 2017/12/20 06:00 PHST- 2017/01/05 00:00 [received] PHST- 2017/07/31 00:00 [accepted] PHST- 2017/12/20 06:00 [entrez] PHST- 2017/12/20 06:00 [pubmed] PHST- 2017/12/20 06:01 [medline] PHST- 2017/11/24 00:00 [pmc-release] AID - 20642 [pii] AID - 10.18632/oncotarget.20642 [doi] PST - epublish SO - Oncotarget. 2017 Sep 5;8(60):101224-101243. doi: 10.18632/oncotarget.20642. eCollection 2017 Nov 24.