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

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

Research output: Contribution to journalArticle

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

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Small Cell Lung Carcinoma
Cell Hypoxia
Cisplatin
CD45 Antigens
Hypoxia-Inducible Factor 1
Tumor Microenvironment
Therapeutic Uses
Therapeutics
Mitogen-Activated Protein Kinases
Small Interfering RNA
Neoplasms
Hypoxia
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ohnishi, H., Yamasaki, A., Nakamura, K., Ichimiya, S., Yanai, K., Umebayashi, M., ... 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

Liprin-α4 as a new therapeutic target for SCLC as an upstream mediator of HIF1α. / Ohnishi, Hideya; Yamasaki, Akio; Nakamura, Katsuya; Ichimiya, Shu; Yanai, Kosuke; Umebayashi, Masayo; Nagai, Shuntaro; Morisaki, Takashi.

In: Anticancer research, Vol. 39, No. 3, 01.03.2019, p. 1179-1184.

Research output: Contribution to journalArticle

Ohnishi, 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, vol. 39, no. 3, pp. 1179-1184. https://doi.org/10.21873/anticanres.13227
Ohnishi, Hideya ; Yamasaki, Akio ; Nakamura, Katsuya ; Ichimiya, Shu ; Yanai, Kosuke ; Umebayashi, Masayo ; Nagai, Shuntaro ; Morisaki, Takashi. / Liprin-α4 as a new therapeutic target for SCLC as an upstream mediator of HIF1α. In: Anticancer research. 2019 ; Vol. 39, No. 3. pp. 1179-1184.
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