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  Separation of low and high grade colon and rectum carcinoma by eukaryotic translation initiation factors 1, 5 and 6

Golob-Schwarzl, N., Schweiger, C., Koller, C., Krassnig, S., Gogg-Kamerer, M., Gantenbein, N., et al. (2017). Separation of low and high grade colon and rectum carcinoma by eukaryotic translation initiation factors 1, 5 and 6. Oncotarget, 8(60), 101224-101243. doi:10.18632/oncotarget.20642.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-F69E-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-F69F-8
Genre: Journal Article

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 Creators:
Golob-Schwarzl, N., Author
Schweiger, C., Author
Koller, C., Author
Krassnig, S., Author
Gogg-Kamerer, M., Author
Gantenbein, N., Author
Toeglhofer, A. M., Author
Wodlej, C., Author
Bergler, H., Author
Pertschy, B., Author
Uranitsch, S., Author
Holter, M., Author
El-Heliebi, A., Author
Fuchs, J., Author
Punschart, A., Author
Stiegler, P., Author
Keil, M., Author
Hoffmann, J., Author
Henderson, D., Author
Lehrach, H.1, Author              
Reinhard, C., AuthorRegenbrecht, C., AuthorSchicho, R., AuthorFickert, P., AuthorLax, S., AuthorHaybaeck, J., Author more..
Affiliations:
1Emeritus Group of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385697              

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Free keywords: PI3K/AKT/mTOR pathway colorectal carcinoma eukaryotic translation initiation factors liver metastases
 Abstract: 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.

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Language(s): eng - English
 Dates: 2017-07-312017-09-05
 Publication Status: Published online
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.18632/oncotarget.20642
ISSN: 1949-2553 (Electronic)
 Degree: -

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Title: Oncotarget
Source Genre: Journal
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Pages: - Volume / Issue: 8 (60) Sequence Number: - Start / End Page: 101224 - 101243 Identifier: ISSN: 1949-2553
CoNE: /journals/resource/1949-2553