Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells

Jung, Jaewon; Hwang, So Young; Hwang, Ji Sun; Oh, Eok Soo; Park, S.-H.; Han, Inn Oc

doi:10.1016/j.ejca.2007.01.034

Cited by 135 publications

(127 citation statements)

References 52 publications

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“…4D). Taken together, these results indicate that the mechanisms responsible for the enhanced cell adhesion in IR cells is distinct from those observed in the cells immediately after irradiation, where levels of FAK phosphorylation, paxillin, and integrin are upregulated (Jung et al, 2007;Wild-Bode et al, 2001).…”

Section: Phosphorylation and Expression Of Other Cell Adhesionrelatedmentioning

confidence: 81%

“…These events occur within 24 h after irradiation and are mediated by increased phosphorylation of p38 and FAK (Jung et al, 2007). In addition, in glioma cells, enhanced integrin expression was found to account for increased cell migration, an early response to irradiation (Wild-Bode et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Jung et al reported that irradiation promoted tumor cell motility and focal adhesion formation, and diminished cell-cell junctions (Jung et al, 2007). These events occur within 24 h after irradiation and are mediated by increased phosphorylation of p38 and FAK (Jung et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Since it has been reported that transient phosphorylation of p38 mediates enhancement of cell motility immediately after irradiation (Jung et al, 2007), we performed an immunoblotting assay to assess p38 phosphorylation (p-p38) in IR cells; unexpectedly, p38 phosphorylation was not significantly different in IR cells and parental cells (Fig. 4A).…”

Section: Phosphorylation and Expression Of Other Cell Adhesionrelatedmentioning

confidence: 99%

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Increased Motility and Invasiveness in Tumor Cells That Survive 10 Gy Irradiation

Tsutsumi

Tsuda

Yazawa

et al. 2009

Cell Struct. Funct.

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ABSTRACT. Radiotherapy is an important noninvasive treatment for many types of cancer. However, it has been reported that the proliferative, invasive, and metastatic capacities of tumor cells can be increased in the repopulated tumors that survive radiotherapy. We have previously established a radiation-surviving cell model for the human non-small cell lung cancer cell line H1299 by harvesting relic cells 14 days after irradiation (IR cells). Here, we report that cell invasion, cell migration, and cell adhesion are enhanced in these surviving cancer cells. The mRNA expression levels of matrix metalloproteinases (MMPs), including mmp1, mmp2, and mmp9, were upregulated in IR cells compared with parental cells. A gelatin zymogram, wound healing assay, and invasion assay showed increased MMP activity, cell motility, and invasiveness in IR cells, respectively. Moreover, IR cells adhered more tightly to collagen-coated dishes than parental cells. Consistently, paxillin, phosphorylated FAK, integrin β1, and vinculin were strongly localized at focal adhesions in IR cells, as visualized by immunofluorescence. In this report, we identify molecules responsible for the malignant properties of tumor cells that survive irradiation. These molecules may be important therapeutic targets for the control of repopulated tumors after radiotherapy.

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Section: Phosphorylation and Expression Of Other Cell Adhesionrelatedmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Phosphorylation and Expression Of Other Cell Adhesionrelatedmentioning

confidence: 99%

See 2 more Smart Citations

Increased Motility and Invasiveness in Tumor Cells That Survive 10 Gy Irradiation

Tsutsumi

Tsuda

Yazawa

et al. 2009

Cell Struct. Funct.

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“…The radiationinduced phenotypic heterogeneity, we report, might reflect transient cellular plasticity as well as stress-evoked responses of preexistent subsets cells seen in the parental DU145 and PC-3 cell populations. [40][41][42][43][44][45][46][47][48][49][50][51][52] Ionizing radiation can promote traits of EMT in normal human mammary epithelium, 41 lung carcinoma 42,43 and colorectal cancer cells. 44 Furthermore, besides their role in E-cadherin repression, 45,46 Slug and Snail have been implicated in radioresistance-associated EMT.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells

et al. 2014

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Fractionated ionizing radiation combined with surgery or hormone therapy represents the first-choice treatment for medium to high-risk localized prostate carcinoma. One of the main reasons for the failure of radiotherapy in prostate cancer is radioresistance and further dissemination of surviving cells. In this study, exposure of four metastasis-derived human prostate cancer cell lines (DU145, PC-3, LNCaP and 22RV1) to clinically relevant daily fractions of ionizing radiation (35 doses of 2 Gy) resulted in generation of two radiation-surviving populations: adherent senescent-like cells expressing common senescenceassociated markers and non-adherent anoikis-resistant stem cell-like cells with active Notch signaling and expression of stem cell markers CD133, Oct-4, Sox2 and Nanog. While a subset of the radiation-surviving adherent cells resumed proliferation shortly after completion of the irradiation regimen, the non-adherent cells started to proliferate only on their reattachment several weeks after the radiation-induced loss of adhesion. Like the parental non-irradiated cells, radiation-surviving re-adherent DU145 cells were tumorigenic in immunocompromised mice. The radiation-induced loss of adhesion was dependent on expression of Snail, as siRNA/shRNA-mediated knockdown of Snail prevented cell detachment. On the other hand, survival of the non-adherent cells required active Erk signaling, as chemical inhibition of Erk1/2 by a MEK-selective inhibitor or Erk1/2 knockdown resulted in anoikis-mediated death in the non-adherent cell fraction. Notably, whereas combined inhibition of Erk and PI3K-Akt signaling triggered cell death in the non-adherent cell fraction and blocked proliferation of the adherent population of the prostate cancer cells, such combined treatment had only marginal if any impact on growth of control normal human diploid cells. These results contribute to better understanding of radiation-induced stress response and heterogeneity of human metastatic prostate cancer cells, document treatment-induced plasticity and phenotypically distinct cell subsets, and suggest the way to exploit their differential sensitivity to radiosensitizing drugs in overcoming radioresistance. Cell Death and Differentiation (2015) 22, 898-911; doi:10.1038/cdd.2014.97; published online 11 July 2014Prostate carcinoma (CaP) is the most frequent type of cancer in men, and the sixth cause of cancer-associated death in men worldwide. 1 Despite the advances in diagnosis and therapy of CaP, the mortality has remained almost unchanged for the last decades. Currently, the most successful treatment for localized CaP is prostatectomy with postoperative fractionated radiotherapy, significantly improving metastasis-free and overall survival, where the median of a 15-year survival is around 47% of patients. 2,3 The rest of the patients develop a metastatic disease that is incurable due to the resistance of CaP to androgen ablation, radiotherapy and chemotherapy. Therefore, understanding the mechanisms of radioresistance and chemoresista...

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Advanced strategies in improving the immunotherapeutic effect of CAR‐T cell therapy

Wang,

Jia,

Dai

et al. 2024

Molecular Oncology

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Chimeric antigen receptor (CAR‐T) cell therapy is a newly developed immunotherapy strategy and has achieved satisfactory outcomes in the treatment of hematological malignancies. However, some adverse effects related to CAR‐T cell therapy have to be resolved before it is widely used in clinics as a cancer treatment. Furthermore, the application of CAR‐T cell therapy in the treatment of solid tumors has been hampered by numerous limitations. Therefore, it is essential to explore novel strategies to improve the therapeutic effect of CAR‐T cell therapy. In this review, we summarized the recently developed strategies aimed at optimizing the generation of CAR‐T cells and improving the anti‐tumor efficiency of CAR‐T cell therapy. Furthermore, the discovery of new targets for CAR‐T cell therapy and the combined treatment strategies of CAR‐T cell therapy with chemotherapy, radiotherapy, cancer vaccines and nanomaterials are highlighted.

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Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells

Cited by 135 publications

References 52 publications

Increased Motility and Invasiveness in Tumor Cells That Survive 10 Gy Irradiation

Increased Motility and Invasiveness in Tumor Cells That Survive 10 Gy Irradiation

Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells

Advanced strategies in improving the immunotherapeutic effect of CAR‐T cell therapy

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