RRC ID 50083
著者 Iida K, Sakai R, Yokoyama S, Kobayashi N, Togo S, Yoshikawa HY, Rawangkan A, Namiki K, Suganuma M.
タイトル Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL.
ジャーナル Sci Rep
Abstract To study the role of cell softening in malignant progression, Transwell assay and atomic force microscope were used to classify six human non-small cell lung cancer cell lines into two groups: a high motility-low stiffness (HMLS) group and a low motility-high stiffness (LMHS) group. We found a significant role of activity of the AXL receptor tyrosine kinase, which belongs to the TAM (Tyro3, AXL, Mer) family, in the stimulation of motility and cell softening. HMLS cells expressed higher AXL levels than LMHS cells and contained phosphorylated AXL. H1703 LMHS cells transfected with exogenous AXL exhibited increased motility and decreased stiffness, with low levels of actin stress fibre formation. Conversely, the AXL-specific inhibitor R428 and AXL-targeting siRNA reduced motility and increased stiffness in H1299 HMLS cells. Knockdown of AXL stimulated actin stress fibre formation, which inhibited tumour formation in a mouse xenograft model. The Ras/Rac inhibitor SCH 51344, which blocks disruption of actin stress fibres, exerted similar effects to AXL inactivation. We therefore propose that the Ras/Rac pathway operates downstream of AXL. Thus, AXL activation-induced cell softening promotes malignant progression in non-small cell lung cancer and represents a key biophysical property of cancer cells.
巻・号 7(1)
ページ 17770
公開日 2017-12-19
DOI 10.1038/s41598-017-18120-4
PII 10.1038/s41598-017-18120-4
PMID 29259259
PMC PMC5736582
MeSH A549 Cells Animals Apoptosis / physiology Axl Receptor Tyrosine Kinase Carcinoma, Non-Small-Cell Lung / metabolism Carcinoma, Non-Small-Cell Lung / pathology Cell Line, Tumor Cell Movement / physiology Cell Proliferation / physiology Disease Progression Female Humans Lung Neoplasms / metabolism* Lung Neoplasms / pathology* Mice Mice, SCID Phosphorylation / physiology Proto-Oncogene Proteins / metabolism* RNA, Small Interfering / metabolism Receptor Protein-Tyrosine Kinases / metabolism* c-Mer Tyrosine Kinase / metabolism
IF 3.998
引用数 5
リソース情報
ヒト・動物細胞 RERF-LC-AI(RCB0444) Lu99(RCB1900)