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) |