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Article

Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E

  • Authors:
    • Victoria Zismanov
    • Oshrat Attar‑Schneider
    • Michael Lishner
    • Rachel Heffez Aizenfeld
    • Shelly Tartakover Matalon
    • Liat Drucker
  • View Affiliations / Copyright

    Affiliations: Oncogenetic Laboratory, Meir Medical Center, Kfar Saba, Israel, Geriatric Department, Meir Medical Center, Kfar Saba, Israel
  • Pages: 860-870
    |
    Published online on: November 24, 2014
       https://doi.org/10.3892/ijo.2014.2774
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Abstract

Intensive protein synthesis is a unique and diffe­rential trait of the multiple myeloma (MM) cells. Previously we showed that tetraspanin overexpression in MM cell lines attenuated mTOR and PI3K cascades, induced protein synthesis, activated unfolded protein response (UPR), and caused autophagic death, all suggesting breach of proteosta­sis. Here we assessed the role of translation initiation in the tetraspanin‑induced MM cell death with emphasis on eIF4E translation initiation factor. We showed tetraspanins attenuated peIF4E and its targets [c‑Myc, cyclin D1 (cycD1)]; eIF4E attenuation was Akt-dependent. eIF4E inhibition in MM cells [bone marrow (BM), lines] by siRNA and/or the anti‑viral drug and competitive eIF4E inhibitor ribavirin (RBV) deleteriously affected MM cells in a similar manner to the overexpression of tetraspanins. Furthermore, combined application of RBV and velcade had a synergistic anti‑MM effect. Our results demonstrate that breach of proteostasis via eIF4E inhibition is an attractive therapeutic approach that may be relatively easily achieved by employing RBV, making this strategy readily translatable into the clinic.
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Copy and paste a formatted citation
Spandidos Publications style
Zismanov V, Attar‑Schneider O, Lishner M, Heffez Aizenfeld R, Tartakover Matalon S and Drucker L: Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E. Int J Oncol 46: 860-870, 2015.
APA
Zismanov, V., Attar‑Schneider, O., Lishner, M., Heffez Aizenfeld, R., Tartakover Matalon, S., & Drucker, L. (2015). Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E. International Journal of Oncology, 46, 860-870. https://doi.org/10.3892/ijo.2014.2774
MLA
Zismanov, V., Attar‑Schneider, O., Lishner, M., Heffez Aizenfeld, R., Tartakover Matalon, S., Drucker, L."Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E". International Journal of Oncology 46.2 (2015): 860-870.
Chicago
Zismanov, V., Attar‑Schneider, O., Lishner, M., Heffez Aizenfeld, R., Tartakover Matalon, S., Drucker, L."Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E". International Journal of Oncology 46, no. 2 (2015): 860-870. https://doi.org/10.3892/ijo.2014.2774
Copy and paste a formatted citation
x
Spandidos Publications style
Zismanov V, Attar‑Schneider O, Lishner M, Heffez Aizenfeld R, Tartakover Matalon S and Drucker L: Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E. Int J Oncol 46: 860-870, 2015.
APA
Zismanov, V., Attar‑Schneider, O., Lishner, M., Heffez Aizenfeld, R., Tartakover Matalon, S., & Drucker, L. (2015). Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E. International Journal of Oncology, 46, 860-870. https://doi.org/10.3892/ijo.2014.2774
MLA
Zismanov, V., Attar‑Schneider, O., Lishner, M., Heffez Aizenfeld, R., Tartakover Matalon, S., Drucker, L."Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E". International Journal of Oncology 46.2 (2015): 860-870.
Chicago
Zismanov, V., Attar‑Schneider, O., Lishner, M., Heffez Aizenfeld, R., Tartakover Matalon, S., Drucker, L."Multiple myeloma proteostasis can be targeted via translation initiation factor eIF4E". International Journal of Oncology 46, no. 2 (2015): 860-870. https://doi.org/10.3892/ijo.2014.2774
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