Liprin-α4 as a New Therapeutic Target for SCLC as an Upstream Mediator of HIF1α

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.

Keywords: HIF1α; Liprin-α4; SCLC; invasion; proliferation.