Dataset Information

MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS/Nrf2/Notch pathway in hepatocellular carcinoma.

ABSTRACT:

Background

Mitochondrial Ca²⁺ plays a critical role in tumorigenesis, including cell proliferation and metastasis. Mitochondrial calcium uniporter regulator 1 (MCUR1) has been shown to be frequently upregulated in HCC and promote cancer cell survival. However, whether MCUR1 is involved in the metastasis of HCC and its underlying mechanisms remain unknown.

Methods

The effect of MCUR1 expression on epithelial-mesenchymal transition (EMT) in HCC cells was first evaluated by immunofluorescent staining and Western blot. Then, in vitro invasion and in vivo metastasis assays were used to evaluate the function of MCUR1 in HCC metastasis. The underlying mechanism has also been explored by investigating the effect of MCUR1 on ROS/Nrf2/Notch1 pathway.

Results

MCUR1 expression was significantly higher in HCC with metastasis and associated with tumor progression. MCUR1 promoted in vitro invasion and in vivo metastasis of HCC cells by promoting EMT via Snail. Mechanistically, MCUR1-mediated mitochondrial Ca²⁺ signaling promoted the EMT of HCC cells by activating ROS/Nrf2/Notch1 pathway. Inhibition of ROS production, mitochondrial Ca²⁺ uptake, Nrf2 expression or Notch1 activity significantly suppressed MCUR1-induced EMT of HCC cells. In addition, treatment with the mitochondrial Ca²⁺-buffering protein parvalbumin significantly inhibited ROS/Nrf2/Notch pathway and MCUR1-induced EMT and HCC metastasis.

Conclusions

Our study provides evidence supporting a metastasis-promoting role for MCUR1-dependent mitochondrial Ca²⁺ uptake in HCC. Our findings suggest that MCUR1 may be a potential therapeutic target for HCC treatment.

SUBMITTER: Jin M

PROVIDER: S-EPMC6434841 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS/Nrf2/Notch pathway in hepatocellular carcinoma.

Jin Mingpeng M Wang Jiaojiao J Ji Xiaoying X Cao Haiyan H Zhu Jianjun J Chen Yibing Y Yang Jin J Zhao Zheng Z Ren Tingting T Xing Jinliang J

Journal of experimental & clinical cancer research : CR 20190325 1

<h4>Background</h4>Mitochondrial Ca<sup>2+</sup> plays a critical role in tumorigenesis, including cell proliferation and metastasis. Mitochondrial calcium uniporter regulator 1 (MCUR1) has been shown to be frequently upregulated in HCC and promote cancer cell survival. However, whether MCUR1 is involved in the metastasis of HCC and its underlying mechanisms remain unknown.<h4>Methods</h4>The effect of MCUR1 expression on epithelial-mesenchymal transition (EMT) in HCC cells was first evaluated b ...[more]

PMID: 30909929

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Dataset Information

MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS/Nrf2/Notch pathway in hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS/Nrf2/Notch pathway in hepatocellular carcinoma.

Similar Datasets

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