TY - JOUR
T1 - Liprin-α4 as a new therapeutic target for SCLC as an upstream mediator of HIF1α
AU - Onishi, Hideya
AU - Yamasaki, Akio
AU - Nakamura, Katsuya
AU - Ichimiya, Shu
AU - Yanai, Kosuke
AU - Umebayashi, Masayo
AU - Nagai, Shuntaro
AU - Morisaki, Takashi
N1 - Funding Information:
The Authors thank Ms. Emi Onishi for skillful technical assistance. This study was supported by JSPS KAKENHI Grant Number 17H04283, 18K08620 and 18K08788.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
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U2 - 10.21873/anticanres.13227
DO - 10.21873/anticanres.13227
M3 - Article
C2 - 30842147
AN - SCOPUS:85062620248
VL - 39
SP - 1179
EP - 1184
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 3
ER -