MTA1 is a novel regulator of autophagy that induces tamoxifen resistance in breast cancer cells

Lee, Minho; Koh, Dahae; Na, Hyelin; Ka, Na-Lee; Kim, Seungsu; Kim, Hyeonji; Hong, Sang Hyun; Shin, Young Kee; Seong, Je Kyung

doi:10.1080/15548627.2017.1388476

Cited by 74 publications

(66 citation statements)

References 48 publications

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“…MiRs increasingly play a potential and core role in the regulation of the malignant development of cancer by acting as oncogenes or tumor suppressors [23]. Furthermore, Lee et al revealed that overexpression of MTA1 was linked to a higher tumor grade and resulted in poorer clinical outcomes in human breast cancer [24]. In this study, we investigated the effect of miR-183 on the invasion and metastasis of NSCLC by mediating MTA1 and found that the up-regulation of miR-183-induced MTA1 restrains the proliferation, EMT, migration and invasion of human NSCLC cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

Yang

Zheng

Yao

et al. 2018

Cell Physiol Biochem

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Backgrounds/Aims: MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. Methods: NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. Results: SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. Conclusion: Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

Yang

Zheng

Yao

et al. 2018

Cell Physiol Biochem

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“…Autophagy, as a cellular process, is very important in cancer research. Recent studies have reported that many anticancer agents kill tumors by inducing autophagic cell death, such as tamoxifen, temozolomide and etoposide . In our previous study, we have found that magnolin suppresses human colorectal cancer cell growth via activating autophagy and cell cycle arrest.…”

Section: Discussionmentioning

confidence: 77%

“…Recent studies have reported that many anticancer agents kill tumors by inducing autophagic cell death, such as tamoxifen, temozolomide and etoposide. [41][42][43] In our previous study, we have found that magnolin suppresses human colorectal cancer cell growth via activating autophagy and cell cycle arrest. Inhibition of autophagy can markedly block magnolin-regulated cell cycle arrest and significantly abrogate magnolin-inhibited proliferation.…”

Section: Discussionmentioning

confidence: 95%

7‐Deoxynarciclasine shows promising antitumor efficacy by targeting Akt against hepatocellular carcinoma

Yin

Qiu

Jin

et al. 2019

Intl Journal of Cancer

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Pretreatment of cells with specific autophagy inhibitor (Bafilomycin A1) or knockdown of endogenous LC-3B by siRNA strongly abrogates 7-DONCS-regulated apoptosis and EMT.Figure 6i: Here, to correct the mistakes above, we have updated the abstract and Figure 6i: Abstract: Pretreatment of cells with specific autophagy inhibitor (Bafilomycin A1) or knockdown of endogenous LC-3B by siRNA strongly enhences 7-DONCS-regulated apoptosis and EMT.

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“…Through investigation in a 3D model, we found TAM at 10 μmol/L slightly increased cell death in non‐invasion cells and had no effect in invasion cells, whereas it induced P62 degradation and mediated U87 cell spheroid autophagy, suggesting that this concentration can induce autophagy and low levels of apoptosis (Figure B). Papers reported that cells treated with TAM induced autophagy and then induced cell apoptosis or death . ER‐α36 was highly expressed at the edge of the sphere, where there was more resistance for TAM than at the center of the sphere (Figures and ).…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor variant ER‐α36 promotes tamoxifen agonist activity in glioblastoma cells

Zhang

et al. 2019

Cancer Science

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Glioblastoma (GBM) is a highly infiltrative and malignant primary brain tumor. Despite aggressive therapy, patients with GBM have a dismal prognosis with median survival of approximately 1 year. Tamoxifen (TAM), a selective estrogen receptor modulator (SERM), has been used to treat GBM for many years. ER‐α36 is a novel variant of estrogen receptor‐alpha66 (ER‐α66) and can mediate cell proliferation through estrogen or anti‐estrogen signaling in different cancer cells. Previously, we found that ER‐α36 was highly expressed in GBM and was involved in the tamoxifen sensitivity of glioblastoma cells. However, the molecular mechanism responsible has not been well established. Here, we found that ER‐α36 is highly expressed in glioblastoma specimens. We further found that ER‐α36 knockdown increased sensitivity of glioblastoma U87 cells to TAM and decreased autophagy in these cells. However, ER‐α36 overexpression decreased TAM sensitivity and induced autophagy. We also established TAM‐resistant glioblastoma U251 cells by a long‐term culture in TAM‐containing medium and found that TAM‐resistant cells showed a six‐fold increase of ER‐α36 mRNA expression and elevated basal autophagy. ER‐α36 knockdown in these TAM‐resistant cells restored TAM sensitivity. In addition, we recapitulated the physiologically relevant tumor microenvironment in an integrated microfluidic device, and U87 cells were treated with a gradient of TAM. We found that ER‐α36 expression is consistent with autophagy protein P62 in a three‐dimensional microenvironment. In summary, these results indicate that ER‐α36 contributes to tamoxifen resistance in glioblastoma cells presumably through regulation of autophagy.

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MTA1 is a novel regulator of autophagy that induces tamoxifen resistance in breast cancer cells

Cited by 74 publications

References 48 publications

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

7‐Deoxynarciclasine shows promising antitumor efficacy by targeting Akt against hepatocellular carcinoma

Estrogen receptor variant ER‐α36 promotes tamoxifen agonist activity in glioblastoma cells

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