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Article

Targeting Insulin-Like Growth Factor 1 Receptor Delays M-Phase Progression and Synergizes with Aurora B Inhibition to Suppress Cell Proliferation

Department of Biochemistry & Molecular Biology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 1058; https://doi.org/10.3390/ijms21031058
Received: 28 January 2020 / Accepted: 1 February 2020 / Published: 5 February 2020
(This article belongs to the Section Molecular Biology)
The insulin-like growth factor 1 receptor (IGF1R) is a receptor-type tyrosine kinase that transduces signals related to cell proliferation, differentiation, and survival. IGF1R expression is often misregulated in tumor cells, but the relevance of this for cancer progression remains unclear. Here, we examined the impact of IGF1R inhibition on cell division. We found that siRNA-mediated knockdown of IGF1R from HeLa S3 cells leads to M-phase delays. Although IGF1R depletion causes partial exclusion of FoxM1 from the nucleus, quantitative real-time PCR revealed that the transcription of M-phase regulators is not affected by decreased levels of IGF1R. Moreover, a similar delay in M phase was observed following 2 h of incubation with the IGF1R inhibitors OSI-906 and NVP-ADW742. These results suggest that the M-phase delay observed in IGF1R-compromised cells is not caused by altered expression of mitotic regulators. Live-cell imaging revealed that both prolonged prometaphase and prolonged metaphase underlie the delay and this can be abrogated by the inhibition of Mps1 with AZ3146, suggesting activation of the Spindle Assembly Checkpoint when IGF1R is inhibited. Furthermore, incubation with the Aurora B inhibitor ZM447439 potentiated the IGF1R inhibitor-induced suppression of cell proliferation, opening up new possibilities for more effective cancer chemotherapy. View Full-Text
Keywords: IGF1R; IGF1; OSI-906; NVP-ADW742; M phase; ZM447439 IGF1R; IGF1; OSI-906; NVP-ADW742; M phase; ZM447439
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MDPI and ACS Style

Yamagishi, A.; Ikeda, Y.; Ikeuchi, M.; Yuki, R.; Saito, Y.; Nakayama, Y. Targeting Insulin-Like Growth Factor 1 Receptor Delays M-Phase Progression and Synergizes with Aurora B Inhibition to Suppress Cell Proliferation. Int. J. Mol. Sci. 2020, 21, 1058. https://doi.org/10.3390/ijms21031058

AMA Style

Yamagishi A, Ikeda Y, Ikeuchi M, Yuki R, Saito Y, Nakayama Y. Targeting Insulin-Like Growth Factor 1 Receptor Delays M-Phase Progression and Synergizes with Aurora B Inhibition to Suppress Cell Proliferation. International Journal of Molecular Sciences. 2020; 21(3):1058. https://doi.org/10.3390/ijms21031058

Chicago/Turabian Style

Yamagishi, Akane, Yuki Ikeda, Masayoshi Ikeuchi, Ryuzaburo Yuki, Youhei Saito, and Yuji Nakayama. 2020. "Targeting Insulin-Like Growth Factor 1 Receptor Delays M-Phase Progression and Synergizes with Aurora B Inhibition to Suppress Cell Proliferation" International Journal of Molecular Sciences 21, no. 3: 1058. https://doi.org/10.3390/ijms21031058

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