Inhibitory effect of the novel tyrosine kinase inhibitor DCC-2036 on triple-negative breast cancer stem cells through AXL-KLF5 positive feedback loop.

ABSTRACT: Triple-negative breast cancer (TNBC), an aggressive histological subtype of breast cancer, exhibits a high risk of early recurrence rate and a poor prognosis, and it is primarily associated with the abundance of cancer stem cells (CSCs). At present, the strategies for effectively eradicating or inhibiting TNBC CSCs are still limited, which makes the development of novel drugs with anti-CSCs function be of great value for the treatment of TNBC, especially the refractory TNBC. In this study, we found that the small-molecule tyrosine kinase inhibitor DCC-2036 suppressed TNBC stem cells by inhibiting the tyrosine kinase AXL and the transcription factor KLF5. DCC-2036 downregulated the expression of KLF5 by decreasing the protein stability of KLF5 via the AXL-Akt-GSK3β signal axis, and in turn,

SUBMITTER: Shen Y 

PROVIDER: S-EPMC9428169 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature