ArticlePloS one2013
Lung cancer cells that survive ionizing radiation show increased integrin α2β1- and EGFR-dependent invasiveness.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- HER2-specific synthetic antigen receptor T cell therapy synergizes with radiotherapy to provide improved antitumor efficacy in non-small cell lung cancer.Journal of leukocyte biology · 2026Article
- A mechanical stimulation-related gene signature predicts prognosis, reflects immune microenvironment remodeling, and identifiesFrontiers in immunology · 2026Article
- α2β1 Integrin specific inhibitor BTT-3033 promotes paclitaxel-induced apoptosis in human ovarian cancer cells.Research in pharmaceutical sciences · 2024Article
- The EGF/EGFR axis and its downstream signaling pathways regulate the motility and proliferation of cultured oral keratinocytes.FEBS open bio · 2023Article
- Effect of mechanical forces on cellular response to radiation.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2022Review
- Mammaglobin 1 mediates progression of trastuzumab-resistant breast cancer cells through regulation of cyclins and NF-κB.FEBS open bio · 2022Article
- Review
- A narrative review of the migration and invasion features of non-small cell lung cancer cells upon xenobiotic exposure: insights fromTranslational lung cancer research · 2021Review
- EGFR-Dependent Extracellular Matrix Protein Interactions Might Light a Candle in Cell Behavior of Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Review
- Effects of radiation on the metastatic process.Molecular medicine (Cambridge, Mass.) · 2018Review
- The Use of PET Imaging for Prognostic Integrin αTheranostics · 2017Article
- X-radiation enhances the collagen type I strap formation and migration potentials of colon cancer cells.Oncotarget · 2016Article
- β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer.International journal of molecular sciences · 2016Article
- Differential response to ablative ionizing radiation in genetically distinct non-small cell lung cancer cells.Cancer biology & therapy · 2016Article
- Bacitracin Inhibits the Migration of U87-MG Glioma Cells via Interferences of the Integrin Outside-in Signaling Pathway.Journal of Korean Neurosurgical Society · 2016Article
- Stiff substrates increase YAP-signaling-mediated matrix metalloproteinase-7 expression.Oncogenesis · 2015Article
- Low-dose photon irradiation alters cell differentiation via activation of hIK channels.Pflugers Archiv : European journal of physiology · 2015Article
- Article
- Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ionizing radiation (IR)-enhanced tumor invasiveness is emerging as a contributor to the limited benefit of radiotherapy; however, its mechanism is still unclear. We previously showed that subcloned lung adenocarcinoma A549 cells (P cells), which survived 10 Gy IR (IR cells), acquired high invasiveness in vitro. Here, we tried to identify the mechanism by which IR cells increase their invasiveness by examining altered gene expression and signaling pathways in IR cells compared with those in P cells. To simulate the microenvironment in vivo, cells were embedded in a three-dimensional (3D) collagen type I gel, in which the IR cells were elongated, while the P cells were spherical. The integrin expression pattern was surveyed, and expression levels of the integrin α2 and β1 subunits were significantly elevated in IR cells. Knockdown of α2 expression or functional blockade of integrin α2β1 resulted in a round morphology of IR cells, and abrogated their invasion in the collagen matrix, suggesting the molecule's essential role in cell spread and invasion in 3D collagen. Epidermal growth factor receptor (EGFR) also presented enhanced expression and activation in IR cells. Treatment with EGFR tyrosine kinase inhibitor, PD168393, decreased the ratio of elongated cells and cell invasiveness. Signaling molecules, including extracellular signal-regulated kinase-1/2 (Erk1/2) and Akt, exhibited higher activation in IR cells. Inhibition of Akt activation by treating with phosphoinositide 3-kinase (PI3K) inhibitor LY294002 decreased IR cell invasion, whereas inhibition of Erk1/2 activation by mitogen-activated protein kinase kinase (MEK) inhibitor U0126 did not. Our results show that integrin α2β1 and EGFR cooperatively promote higher invasiveness of IR-survived lung cancer cells, mediated in part by the PI3K/Akt signaling pathway, and might serve as alternative targets in combination with radiotherapy.
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