Small Cell Lung Carcinoma Cells Depend on KIF11 for Survival

Author:

Sakuma Yuji1ORCID,Hirai Sachie1,Yamaguchi Miki1,Idogawa Masashi2ORCID

Affiliation:

1. Department of Molecular Medicine, Research Institute for Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan

2. Department of Medical Genome Sciences, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan

Abstract

Few efficacious treatment options are available for patients with small cell lung carcinoma (SCLC), indicating the need to develop novel therapeutic approaches. In this study, we explored kinesin family member 11 (KIF11), a potential therapeutic target in SCLC. An analysis of publicly available data suggested that KIF11 mRNA expression levels are significantly higher in SCLC tissues than in normal lung tissues. When KIF11 was targeted by RNA interference or a small-molecule inhibitor (SB743921) in two SCLC cell lines, Lu-135 and NCI-H69, cell cycle progression was arrested at the G2/M phase with complete growth suppression. Further work suggested that the two cell lines were more significantly affected when both KIF11 and BCL2L1, an anti-apoptotic BCL2 family member, were inhibited. This dual inhibition resulted in markedly decreased cell viability. These findings collectively indicate that SCLC cells are critically dependent on KIF11 activity for survival and/or proliferation, as well as that KIF11 inhibition could be a new strategy for SCLC treatment.

Funder

Grants-in-Aid for Scientific Research from JSPS

Publisher

MDPI AG

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