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Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth
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| Zeitschriftentitel: | Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , , |
| In: | Cancer Research, 80, 2020, 2, S. 319-333 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Qu, Yuan-Yuan Zhao, Rui Zhang, Hai-Liang Zhou, Qian Xu, Fu-Jiang Zhang, Xuan Xu, Wen-Hao Shao, Ning Zhou, Shu-Xian Dai, Bo Zhu, Yao Shi, Guo-Hai Shen, Yi-Jun Zhu, Yi-Ping Han, Cheng-Tao Chang, Kun Lin, Yan Zang, Wei-Dong Xu, Wei Ye, Ding-Wei Zhao, Shi-Min Zhao, Jian-Yuan Qu, Yuan-Yuan Zhao, Rui Zhang, Hai-Liang Zhou, Qian Xu, Fu-Jiang Zhang, Xuan Xu, Wen-Hao Shao, Ning Zhou, Shu-Xian Dai, Bo Zhu, Yao Shi, Guo-Hai Shen, Yi-Jun Zhu, Yi-Ping Han, Cheng-Tao Chang, Kun Lin, Yan Zang, Wei-Dong Xu, Wei Ye, Ding-Wei Zhao, Shi-Min Zhao, Jian-Yuan |
|---|---|
| author |
Qu, Yuan-Yuan Zhao, Rui Zhang, Hai-Liang Zhou, Qian Xu, Fu-Jiang Zhang, Xuan Xu, Wen-Hao Shao, Ning Zhou, Shu-Xian Dai, Bo Zhu, Yao Shi, Guo-Hai Shen, Yi-Jun Zhu, Yi-Ping Han, Cheng-Tao Chang, Kun Lin, Yan Zang, Wei-Dong Xu, Wei Ye, Ding-Wei Zhao, Shi-Min Zhao, Jian-Yuan |
| spellingShingle |
Qu, Yuan-Yuan Zhao, Rui Zhang, Hai-Liang Zhou, Qian Xu, Fu-Jiang Zhang, Xuan Xu, Wen-Hao Shao, Ning Zhou, Shu-Xian Dai, Bo Zhu, Yao Shi, Guo-Hai Shen, Yi-Jun Zhu, Yi-Ping Han, Cheng-Tao Chang, Kun Lin, Yan Zang, Wei-Dong Xu, Wei Ye, Ding-Wei Zhao, Shi-Min Zhao, Jian-Yuan Cancer Research Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth Cancer Research Oncology |
| author_sort |
qu, yuan-yuan |
| spelling |
Qu, Yuan-Yuan Zhao, Rui Zhang, Hai-Liang Zhou, Qian Xu, Fu-Jiang Zhang, Xuan Xu, Wen-Hao Shao, Ning Zhou, Shu-Xian Dai, Bo Zhu, Yao Shi, Guo-Hai Shen, Yi-Jun Zhu, Yi-Ping Han, Cheng-Tao Chang, Kun Lin, Yan Zang, Wei-Dong Xu, Wei Ye, Ding-Wei Zhao, Shi-Min Zhao, Jian-Yuan 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-19-1023 <jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)–GATA-binding protein 3 (GATA3)–enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK–GATA3–ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK–GATA3–ECHS1 pathway as a potential therapeutic target and prognostic biomarker.</jats:p> </jats:sec> Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth Cancer Research |
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10.1158/0008-5472.can-19-1023 |
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American Association for Cancer Research (AACR), 2020 |
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American Association for Cancer Research (AACR), 2020 |
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0008-5472 1538-7445 |
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| title |
Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_unstemmed |
Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_full |
Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_fullStr |
Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_full_unstemmed |
Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_short |
Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_sort |
inactivation of the ampk–gata3–echs1 pathway induces fatty acid synthesis that promotes clear cell renal cell carcinoma growth |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/0008-5472.can-19-1023 |
| publishDate |
2020 |
| physical |
319-333 |
| description |
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title />
<jats:p>The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)–GATA-binding protein 3 (GATA3)–enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK–GATA3–ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Significance:</jats:title>
<jats:p>These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK–GATA3–ECHS1 pathway as a potential therapeutic target and prognostic biomarker.</jats:p>
</jats:sec> |
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| author | Qu, Yuan-Yuan, Zhao, Rui, Zhang, Hai-Liang, Zhou, Qian, Xu, Fu-Jiang, Zhang, Xuan, Xu, Wen-Hao, Shao, Ning, Zhou, Shu-Xian, Dai, Bo, Zhu, Yao, Shi, Guo-Hai, Shen, Yi-Jun, Zhu, Yi-Ping, Han, Cheng-Tao, Chang, Kun, Lin, Yan, Zang, Wei-Dong, Xu, Wei, Ye, Ding-Wei, Zhao, Shi-Min, Zhao, Jian-Yuan |
| author_facet | Qu, Yuan-Yuan, Zhao, Rui, Zhang, Hai-Liang, Zhou, Qian, Xu, Fu-Jiang, Zhang, Xuan, Xu, Wen-Hao, Shao, Ning, Zhou, Shu-Xian, Dai, Bo, Zhu, Yao, Shi, Guo-Hai, Shen, Yi-Jun, Zhu, Yi-Ping, Han, Cheng-Tao, Chang, Kun, Lin, Yan, Zang, Wei-Dong, Xu, Wei, Ye, Ding-Wei, Zhao, Shi-Min, Zhao, Jian-Yuan, Qu, Yuan-Yuan, Zhao, Rui, Zhang, Hai-Liang, Zhou, Qian, Xu, Fu-Jiang, Zhang, Xuan, Xu, Wen-Hao, Shao, Ning, Zhou, Shu-Xian, Dai, Bo, Zhu, Yao, Shi, Guo-Hai, Shen, Yi-Jun, Zhu, Yi-Ping, Han, Cheng-Tao, Chang, Kun, Lin, Yan, Zang, Wei-Dong, Xu, Wei, Ye, Ding-Wei, Zhao, Shi-Min, Zhao, Jian-Yuan |
| author_sort | qu, yuan-yuan |
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| container_title | Cancer Research |
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| description | <jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)–GATA-binding protein 3 (GATA3)–enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK–GATA3–ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK–GATA3–ECHS1 pathway as a potential therapeutic target and prognostic biomarker.</jats:p> </jats:sec> |
| doi_str_mv | 10.1158/0008-5472.can-19-1023 |
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| imprint | American Association for Cancer Research (AACR), 2020 |
| imprint_str_mv | American Association for Cancer Research (AACR), 2020 |
| institution | DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15 |
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| physical | 319-333 |
| publishDate | 2020 |
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| spelling | Qu, Yuan-Yuan Zhao, Rui Zhang, Hai-Liang Zhou, Qian Xu, Fu-Jiang Zhang, Xuan Xu, Wen-Hao Shao, Ning Zhou, Shu-Xian Dai, Bo Zhu, Yao Shi, Guo-Hai Shen, Yi-Jun Zhu, Yi-Ping Han, Cheng-Tao Chang, Kun Lin, Yan Zang, Wei-Dong Xu, Wei Ye, Ding-Wei Zhao, Shi-Min Zhao, Jian-Yuan 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-19-1023 <jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)–GATA-binding protein 3 (GATA3)–enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK–GATA3–ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK–GATA3–ECHS1 pathway as a potential therapeutic target and prognostic biomarker.</jats:p> </jats:sec> Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth Cancer Research |
| spellingShingle | Qu, Yuan-Yuan, Zhao, Rui, Zhang, Hai-Liang, Zhou, Qian, Xu, Fu-Jiang, Zhang, Xuan, Xu, Wen-Hao, Shao, Ning, Zhou, Shu-Xian, Dai, Bo, Zhu, Yao, Shi, Guo-Hai, Shen, Yi-Jun, Zhu, Yi-Ping, Han, Cheng-Tao, Chang, Kun, Lin, Yan, Zang, Wei-Dong, Xu, Wei, Ye, Ding-Wei, Zhao, Shi-Min, Zhao, Jian-Yuan, Cancer Research, Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth, Cancer Research, Oncology |
| title | Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_full | Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_fullStr | Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_full_unstemmed | Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_short | Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| title_sort | inactivation of the ampk–gata3–echs1 pathway induces fatty acid synthesis that promotes clear cell renal cell carcinoma growth |
| title_unstemmed | Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/0008-5472.can-19-1023 |