Open AccessThe tyrosine kinase v‐Src modifies cytotoxicities of anticancer drugs targeting cell division
Author(s) -
Yuki Ryuzaburo,
Hagino Mari,
Ueno Sachi,
Kuga Takahisa,
Saito Youhei,
Fukumoto Yasunori,
Yamaguchi Noritaka,
Yamaguchi Naoto,
Nakayama Yuji
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16270
Subject(s) - proto oncogene tyrosine protein kinase src , tyrosine kinase , microbiology and biotechnology , cancer research , mitosis , biology , cancer cell , cell cycle , chemistry , kinase , cell , cancer , signal transduction , biochemistry , genetics
v‐Src oncogene causes cell transformation through its strong tyrosine kinase activity. We have revealed that v‐Src‐mediated cell transformation occurs at a low frequency and it is attributed to mitotic abnormalities‐mediated chromosome instability. v‐Src directly phosphorylates Tyr‐15 of cyclin‐dependent kinase 1 (CDK1), thereby causing mitotic slippage and reduction in Eg5 inhibitor cytotoxicity. However, it is not clear whether v‐Src modifies cytotoxicities of the other anticancer drugs targeting cell division. In this study, we found that v‐Src restores cancer cell viability reduced by various microtubule‐targeting agents (MTAs), although v‐Src does not alter cytotoxicity of DNA‐damaging anticancer drugs. v‐Src causes mitotic slippage of MTAs‐treated cells, consequently generating proliferating tetraploid cells. We further demonstrate that v‐Src also restores cell viability reduced by a polo‐like kinase 1 (PLK1) inhibitor. Interestingly, treatment with Aurora kinase inhibitor strongly induces cell death when cells express v‐Src. These results suggest that the v‐Src modifies cytotoxicities of anticancer drugs targeting cell division. Highly activated Src‐induced resistance to MTAs through mitotic slippage might have a risk to enhance the malignancy of cancer cells through the increase in chromosome instability upon chemotherapy using MTAs.