DataVXAdvanced SciencePaper
journal article·2023-07Open access

The c‐Src/LIST Positive Feedback Loop Sustains Tumor Progression and Chemoresistance

Xianteng Wang, Bing Wang, Fang Li, Xingkai Li, Ting Guo, Yushun Gao, Dawei Wang, Weiren Huang

Advanced Science· Volume 10· Issue 20
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Source abstract

Abstract

Abstract Chemotherapy resistance and treatment failure hinder clinical cancer treatment. Src, the first mammalian proto‐oncogene to be discovered, is a valuable anti‐cancer therapeutic target. Although several c‐Src inhibitors have reached the clinical stage, drug resistance remains a challenge during treatment. Herein, a positive feedback loop between a previously uncharacterized long non‐coding RNA (lncRNA), which the authors renamed lncRNA‐inducing c‐Src tumor‐promoting function (LIST), and c‐Src is uncovered. LIST directly binds to and regulates the Y530 phosphorylation activity of c‐Src. As a c‐Src agonist, LIST promotes tumor chemoresistance and progression in vitro and in vivo in multiple cancer types. c‐Src can positively regulate LIST transcription by activating the NF‐κB signaling pathway and then recruiting the P65 transcription factor to the LIST promoter. Interestingly, the LIST/c‐Src interaction is associated with evolutionary new variations of c‐Src. It is proposed that the human‐specific LIST/c‐Src axis renders an extra layer of control over c‐Src activity. Additionally, the LIST/c‐Src axis is of high physiological relevance in cancer and may be a valuable prognostic biomarker and potential therapeutic target.
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Research context

OpenAlex topics: Cancer-related molecular mechanisms research · RNA Research and Splicing · NF-κB Signaling Pathways

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Urology Shenzhen Institute of Translational Medicine Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging National‐Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering Shenzhen University Medical school Shenzhen 518060 China

Shenzhen Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China

Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University Shenzhen 518035 China

Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China

Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital Chinese Academy of Medical Sciences Langfang 065001 China

Department of Thoracic Surgery Chifeng Municipal Hospital Chifeng 024000 China

Funding

National Natural Science Foundation of China · Wu Jieping Medical Foundation

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