Liprin-α4 as a new therapeutic target for SCLC as an upstream mediator of HIF1α

Hideya Onishi, Akio Yamasaki, Katsuya Nakamura, Shu Ichimiya, Kosuke Yanai, Masayo Umebayashi, Shuntaro Nagai, Takashi Morisaki

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Abstract

Background/Aim: Small-cell lung cancer (SCLC) remains one of deadliest types of cancers. Cis-diamminedichloroplatinum (CDDP) is a key chemotherapeutic agent for SCLC, however, its therapeutic effect is limited. Recently, hypoxia in the cancer microenvironment has been suggested to influence the effect of cancer therapy. Materials and Methods: Using small interfering RNA inhibition of leukocyte common antigen-related interacting protein alpha 4 (liprin-α4), and of hypoxia-inducible factor (HIF)-1α, proliferation, invasion, migration and chemosensitivity were investigated in SBC-5 SCLC cells, under normoxia and hypoxia. Results: Liprin-α4 was found to contribute to proliferation, but not migration and invasion of SBC-5 cells both under normoxia and hypoxia. Inhibition of liprin-α4 increased chemosensitivity of SBC-5 cells under hypoxia. Liprin-α4 signaling occurs through mitogen-activated protein kinase pathways via activation of HIF1α expression. Inhibition of HIF1α reduced proliferation and increased chemosensitivity of SBC-5 cells under hypoxia. Conclusion: Liprin-α4 inhibition may enhance the effect of CDDP and liprin-α4 might be a novel therapeutic target in SCLC.

Original languageEnglish
Pages (from-to)1179-1184
Number of pages6
JournalAnticancer research
Volume39
Issue number3
DOIs
Publication statusPublished - Mar 1 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Onishi, H., Yamasaki, A., Nakamura, K., Ichimiya, S., Yanai, K., Umebayashi, M., Nagai, S., & Morisaki, T. (2019). Liprin-α4 as a new therapeutic target for SCLC as an upstream mediator of HIF1α. Anticancer research, 39(3), 1179-1184. https://doi.org/10.21873/anticanres.13227