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MTA1, a Novel ATP Synthase Complex Modulator, Enhances Colon Cancer Liver Metastasis by Driving Mitochondrial Metabolism Reprogramming

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العنوان: MTA1, a Novel ATP Synthase Complex Modulator, Enhances Colon Cancer Liver Metastasis by Driving Mitochondrial Metabolism Reprogramming
بيانات النشر: Wiley 2023
تفاصيل مُضافة: Wang, Ting
Sun, Fangzhou
Li, Chunxiao
Nan, Peng
Song, Yan
Wan, Xuhao
Mo, Hongnan
Wang, Jinsong
Zhou, Yantong
Guo, Yuzheng
Helali, Aya Ei
Xu, Dongkui
Zhan, Qimin
Ma, Fei
Qian, Haili
نوع الوثيقة: Electronic Resource
مستخلص: Liver metastasis is the most fatal event of colon cancer patients. Warburg effect has been long challenged by the fact of upregulated oxidative phosphorylation (OXPHOS), while its mechanism remains unclear. Here, metastasis-associated antigen 1 (MTA1) is identified as a newly identified adenosine triphosphate (ATP) synthase modulator by interacting with ATP synthase F1 subunit alpha (ATP5A), facilitates colon cancer liver metastasis by driving mitochondrial bioenergetic metabolism reprogramming, enhancing OXPHOS; therefore, modulating ATP synthase activity and downstream mTOR pathways. High-throughput screening of an anticancer drug shows MTA1 knockout increases the sensitivity of colon cancer to mitochondrial bioenergetic metabolism-targeted drugs and mTOR inhibitors. Inhibiting ATP5A enhances the sensitivity of liver-metastasized colon cancer to sirolimus in an MTA1-dependent manner. The therapeutic effects are verified in xenograft models and clinical cases. This research identifies a new modulator of mitochondrial bioenergetic reprogramming in cancer metastasis and reveals a new mechanism on upregulating mitochondrial OXPHOS as the reversal of Warburg effect in cancer metastasis is orchestrated.
مصطلحات الفهرس: Adenosine triphosphate (ATP), Colorectal cancer, Mitochondrial glucose metabolism, Metastasis-associated antigen 1 (MTA1), MTOR inhibitors, Article
URL: https://repository.hkust.edu.hk/ir/Record/1783.1-128241Test
https://doi.org/10.1002/advs.202300756Test
http://lbdiscover.ust.hk/uresolver?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rfr_id=info:sid/HKUST:SPI&rft.genre=article&rft.issn=2198-3844&rft.volume=&rft.issue=&rft.date=2023&rft.spage=&rft.aulast=Wang&rft.aufirst=&rft.atitle=MTA1%2C+a+Novel+ATP+Synthase+Complex+Modulator%2C+Enhances+Colon+Cancer+Liver+Metastasis+by+Driving+Mitochondrial+Metabolism+Reprogramming&rft.title=ADVANCED+SCIENCETest
http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=LinksAMR&SrcApp=PARTNER_APP&DestLinkType=FullRecord&DestApp=WOS&KeyUT=001027203300001Test
http://www.scopus.com/record/display.url?eid=2-s2.0-85164700632&origin=inwardTest
الإتاحة: Open access content. Open access content
ملاحظة: English
أرقام أخرى: HNK oai:repository.hkust.edu.hk:1783.1-128241
Advanced Science, July 2023, article number 2300756
2198-3844
1394209637
المصدر المساهم: HONG KONG UNIV OF SCI & TECH, THE
From OAIster®, provided by the OCLC Cooperative.
رقم الانضمام: edsoai.on1394209637
قاعدة البيانات: OAIster
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