HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation

  • Authors:
    • Bing Chen
    • Jin Zhao
    • Shengbin Zhang
    • Yonggang Zhang
    • Zonghai Huang
  • View Affiliations

  • Published online on: October 11, 2016     https://doi.org/10.3892/or.2016.5157
  • Pages: 3664-3672
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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 suppre­ssed 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.
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December-2016
Volume 36 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Chen B, Zhao J, Zhang S, Zhang Y and Huang Z: HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation. Oncol Rep 36: 3664-3672, 2016
APA
Chen, B., Zhao, J., Zhang, S., Zhang, Y., & Huang, Z. (2016). HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation. Oncology Reports, 36, 3664-3672. https://doi.org/10.3892/or.2016.5157
MLA
Chen, B., Zhao, J., Zhang, S., Zhang, Y., Huang, Z."HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation". Oncology Reports 36.6 (2016): 3664-3672.
Chicago
Chen, B., Zhao, J., Zhang, S., Zhang, Y., Huang, Z."HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation". Oncology Reports 36, no. 6 (2016): 3664-3672. https://doi.org/10.3892/or.2016.5157