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 language | English |
|---|---|
| Pages (from-to) | 1179-1184 |
| Number of pages | 6 |
| Journal | Anticancer research |
| Volume | 39 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2019 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Liprin-α4 as a new therapeutic target for SCLC as an upstream mediator of HIF1α. / Onishi, 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 journal › Article
}
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
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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UR - http://www.scopus.com/inward/citedby.url?scp=85062620248&partnerID=8YFLogxK
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 -