EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition

Kim, Song Hee; Lee, Won Hyeok; Kim, Seong Who; Je, Hyoung Uk; Lee, Mi Kyung; Chang, Hyo Won; Kim, Young Min; Kim, Kyungbin; Kim, Sang Yoon; Han, Myung Woul

doi:10.1016/j.cellsig.2018.04.001

Cited by 13 publications

(17 citation statements)

References 36 publications

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“…Some contradictory results underline the complexity of Eph receptor biology in cancer settings, and EPHA3 does not play a major role in lung and colorectal tumorigenesis [20,21]. However, we demonstrated previously that EPHA3 is overexpressed in radioresistant head and neck cancer, plays a crucial role in the development of radioresistance in head and neck cancers, and can regulate the epithelial mesenchymal transition pathway through the PTEN/Akt signal pathway [15]. Based on these previous findings, we focused on the epigenetic regulation of PTEN as related to radioresistance by EPHA3 in the present study.…”

Section: Introductionmentioning

confidence: 85%

“…An isogenic model of successively irradiated AMC HN3R cells was established after the cells received a cumulative dose of 70 Gy. This model was originally designed to investigate radioresistance, using cells of the same origin that differ only in terms of their radiosensitivity [15,30,31]. Previously, we performed a microarray expression data analysis in AMC HN3 and HN3R.…”

Section: Cell Culture and Establishment Of Radioresistant Head And Nementioning

confidence: 99%

“…Previously, we performed a microarray expression data analysis in AMC HN3 and HN3R. We identified the EPHA3 overexpression in AMC HN3R and revealed that EPHA3 has an important role in radioresistance [15]. We prepared various additional radioresistant head and neck cancer cell lines (HN 31R cell line, MDA-MB-231R cell line) using the same procedure.…”

Section: Cell Culture and Establishment Of Radioresistant Head And Nementioning

confidence: 99%

“…EPHA3 is overexpressed in various cancers, such as glioblastoma, gastric cancer, and prostate cancer, and has an important role in tumorigenesis, aggressiveness, and radioresistance [15][16][17][18][19]. Some contradictory results underline the complexity of Eph receptor biology in cancer settings, and EPHA3 does not play a major role in lung and colorectal tumorigenesis [20,21].…”

Section: Introductionmentioning

confidence: 99%

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EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

et al. 2021

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EPHA3, a member of the EPH family, is overexpressed in various cancers. We demonstrated previously that EPHA3 is associated with radiation resistance in head and neck cancer via the PTEN/Akt/EMT pathway; the inhibition of EPHA3 significantly enhances the efficacy of radiotherapy in vitro and in vivo. In this study, we investigated the mechanisms of PTEN regulation through EPHA3-related signaling. Increased DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2) levels, along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, correlated with decreased levels of PTEN in radioresistant head and neck cancer cells. Furthermore, PTEN is regulated in two ways: DNMT1-mediated DNA methylation, and EZH2-mediated histone methylation through EPHA3/C-myc signaling. Our results suggest that EPHA3 could display a novel regulatory mechanism for the epigenetic regulation of PTEN in radioresistant head and neck cancer cells.

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Section: Introductionmentioning

confidence: 85%

Section: Cell Culture and Establishment Of Radioresistant Head And Nementioning

confidence: 99%

Section: Cell Culture and Establishment Of Radioresistant Head And Nementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

et al. 2021

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“…EMT process and HGF/c-MET pathway are foremost molecular mechanisms of antitumor drug resistance, which significantly promotes the antitumor effect of drugs on cancer cells. [67][68][69][70][71][72][73][74][75][76][77] Jiao et al showed that HGF treatment induced gefitinib resistance in human lung cancer cells and miR-1-3 p or miR-206 sensitizes cells to gefitinib by inhibition of c-Met and EMT process. 78 In the present work, we found that ARQ-197 inhibited the EMT process of HCC cells and enhanced the sensitivity of HCC cells to sorafenib.…”

Section: Discussionmentioning

confidence: 99%

<p>ARQ-197 enhances the antitumor effect of sorafenib in hepatocellular carcinoma cells via decelerating its intracellular clearance</p>

Gao¹,

Chen²,

Huang³

et al. 2019

OTT

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Background: Hepatocellular carcinoma (HCC) is one of the heaviest malignant burdens in China. Molecular targeting agent, sorafenib, is the main therapeutic option for antitumor therapy of advanced HCC, but it is currently too expensive for the public and its therapeutic effect does not satisfy initial expectation. Therefore, it is important to develop more effective molecular targeted therapeutic strategies for advanced HCC. Materials and methods: The antitumor effects of sorafenib or ARQ-197, an antagonist of c-MET (tyrosine-protein kinase Met or hepatocyte growth factor receptor), were examined by MTT or in murine tumor model. The effect of ARQ-197 on epithelial-mesenchymal transition (EMT) or multidrug resistance (MDR) was examined by quantitative real-time PCR for the expression of related genes. The clearance of sorafenib in HCC cells was detected by liquid chromatography-mass spectrometry/mass spectrometry. Results: ARQ-197 treatment enhanced the sensitivity of HCC cells to sorafenib. Mechanistic studies indicated that ARQ-197 inhibited the expression of EMT-and MDR-related genes. Moreover, ARQ-197 treatment decelerated the clearance of sorafenib in cultured HCC cells and subcutaneous HCC tumors in nude mice. Conclusion: In the present work, our data suggested that ARQ-197 decelerated the clearance of sorafenib in HCC cells and enhanced the antitumor effect of sorafenib.

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EphA3 is up-regulated by epidermal growth factor and promotes formation of glioblastoma cell aggregates

Toyama

Hamaoka

Katoh

2019

Biochemical and Biophysical Research Communications

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EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition

Cited by 13 publications

References 36 publications

EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

<p>ARQ-197 enhances the antitumor effect of sorafenib in hepatocellular carcinoma cells via decelerating its intracellular clearance</p>

EphA3 is up-regulated by epidermal growth factor and promotes formation of glioblastoma cell aggregates

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