Carbon Ion Irradiation Suppresses Metastatic Potential of Human Non-small Cell Lung Cancer A549 Cells through the Phosphatidylinositol-3-Kinase/Akt Signaling Pathway

Ogata, Toshiyuki; Teshima, Teruki; Inaoka, Miho; Minami, Kazumasa; Tsuchiya, T.; Isono, Motohide; Furusawa, Yoshiya; Matsuura, Nariaki

doi:10.1269/jrr.10102

Cited by 59 publications

(45 citation statements)

References 18 publications

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“…As we proved that ANLN-targeting siRNA was effective at inhibiting cancer cell growth and invasion, ANLN might become a candidate target for development of anticancer drugs. It was reported that carbon-ion beam irradiation effectively suppressed metastatic potential of lung cancer cells along with the reduced expression of ANLN, which indicated that expression level of ANLN could also be a potential maker for evaluation of cancer therapeutic efficacy 29, 30 . As patients with NMIBC have lifelong risk of recurrence and progression, ANLN could be a potential biomarker for stratifying the aggressiveness of BLCA.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

Zeng

et al. 2017

Sci Rep

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The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p = 0.001), progression-free (median, 19.7 vs. 27.9 months, p = 0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p = 0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

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Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

Zeng

et al. 2017

Sci Rep

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“…Hadrontherapy was found to decrease migration and invasion in several studies [13, 52], but no data exists in HNSCC location. Ogata T et al were the first to introduce heavy ion species in reduction of cell motility [53].…”

Section: Discussionmentioning

confidence: 99%

“…Ogata T et al were the first to introduce heavy ion species in reduction of cell motility [53]. Carbon ion irradiation would block cell motility pathways, decreasing integrins' secretion [54], particularly MMP-2 secretion [52], or Akt phosphorylation [55] in contrast to photon irradiation. In a medulloblastoma cell line, Rieken S el al.…”

Section: Discussionmentioning

confidence: 99%

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

et al. 2016

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Cancer Stem Cells (CSCs) in Head and Neck Squamous Cell Carcinoma (HNSCC) have extremely aggressive profile (high migratory and invasive potential). These characteristics can explain their resistance to conventional treatment. Efficacy of photon and carbon ion irradiation with addition of cetuximab (5 nM) is studied on clonogenic death, migration and invasion of two HNSCC populations: SQ20B and SQ20B/CSCs. SQ20B express E-cadherin and overexpress EGFR while SQ20B/CSCs express N-cadherin and low EGFR. Cetuximab strongly inhibits SQ20B proliferation but has no effect on SQ20B/CSCs. 2 Gy photon irradiation enhances migration and invasiveness in both populations (p < 0.05), while cetuximab only stops SQ20B migration (p < 0.005). Carbon irradiation significantly inhibits invasion in both populations (p < 0.05), and the association with cetuximab significantly inhibits invasion in both populations (p < 0.005). These results highlight CSCs characteristics: EGFRLow, cetuximab-resistant, and highly migratory. Carbon ion irradiation appears to be a very promising therapeutic modality counteracting migration/invasion process in both parental cells and CSCs in contrast to photon irradiation.

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“…The tyrosine phosphorylation of EGFR leads to the activation of many signaling pathways through the recruitment of diverse proteins. For example, AKT acts downstream of phosphatidylinositol-3 kinase to regulate tumor cell proliferation and invasion [37]. At the same time, the RAF-mitogen-activated protein kinase-ERK pathway can also communicate signals from EGFR on the surface to the DNA in the nucleus of the cell.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐133b inhibits the growth of non‐small‐cell lung cancer by targeting the epidermal growth factor receptor

et al. 2012

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Both the deregulation of microRNAs and epidermal growth factor receptor (EGFR) are emerging as important factors in non‐small‐cell lung cancer (NSCLC). Here, miR‐133b was found to be associated with tumor stage, the extent of regional lymph node involvement, stage, visceral pleura or vessel invasion and EGFR mRNA expression in Chinese patients with NSCLC. Bioinformatic analysis and luciferase reporter assay revealed that miR‐133b can interact specifically with the 3′‐UTR of EGFR mRNA. Functionally, miR‐133b transfection showed regulatory activity in translationally repressing EGFR mRNA. Moreover, miR‐133b transfection may modulate apoptosis, invasion and sensitivity to EGFR‐TKI through the EGFR signaling pathways, especially in EGFR‐addicted NSCLC cells. Taken together, our findings show that miR‐133b can inhibit cell growth of NSCLC through targeting EGFR and regulating its downstream signaling pathway. This finding has important implications for the development of targeted therapeutics for a number of EGFR‐addicted cancers.

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Carbon Ion Irradiation Suppresses Metastatic Potential of Human Non-small Cell Lung Cancer A549 Cells through the Phosphatidylinositol-3-Kinase/Akt Signaling Pathway

Cited by 59 publications

References 18 publications

Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

MicroRNA‐133b inhibits the growth of non‐small‐cell lung cancer by targeting the epidermal growth factor receptor

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