Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer.

ABSTRACT:

Background

Tyrosine kinase inhibitors (TKIs) have demonstrated clinical benefits in the treatment of several tumour types. However, the emergence of TKI resistance restricts the therapeutic effect. This study uses non-small cell lung cancer (NSCLC) to explore the mechanisms contributing to TKI resistance in tumours.

Methods

Biological phenotypes and RNA microarray expression data were analysed in NSCLC cells with and without TKI pretreatment. Specific inhibitors and siRNAs were used to validate the direct involvement of an AKT/FOXM1/STMN1 pathway in TKI resistance. Patients' tissues were analysed to explore the clinical importance of FOXM1 and STMN1.

Results

In vitro and in vivo studies showed that TKIs induced the enrichment of cancer stem cells (CSC), promoted epith

SUBMITTER: Li M 

PROVIDER: S-EPMC5625681 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature