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Downregulation of pro-surfactant protein B contributes to the recurrence of early-stage non-small cell lung cancer by activating PGK1-mediated Akt signaling

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机构: [1]Chongqing Univ, Sch Med, Chongqing 400030, Peoples R China [2]Army Med Univ, Daping Hosp, Canc Ctr, Chongqing 400042, Peoples R China [3]Chinese Peoples Liberat Army Gen Hosp, Coll Pulm & Crit Care Med, Beijing, Peoples R China [4]Army Med Univ, Daping Hosp, Dept Thorac Surg, Chongqing 400042, Peoples R China [5]Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sichuan Canc Ctr, Chengdu 610041, Peoples R China [6]Army Med Univ, Daping Hosp, State Key Lab Trauma Burn & Combined Injury, Chongqing 400042, Peoples R China [7]Chongqing Univ, Canc Hosp, Chongqing Key Lab Intelligent Oncol Breast Canc, Chongqing 400030, Peoples R China
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关键词: Recurrence Early-stage NSCLC Pro-SFTPB PGK1 Akt pathway

摘要:
Recurrence is one of the main causes of treatment failure in early-stage non-small cell lung cancer (NSCLC). However, there are no predictors of the recurrence of early-stage NSCLC, and the molecular mechanism of its recurrence is not clear. In this study, we used clinical sample analysis to demonstrate that low levels of expression of precursor surfactant protein B (pro-SFTPB) in primary NSCLC tissue compared to their adjacent tissues are closely correlated with recurrence and poor prognosis in early-stage NSCLC patients. In vitro and in vivo experiments showed that downregulation of pro-SFTPB expression activates the Akt pathway by upregulating PGK1, which promotes metastasis and tumorigenicity in NSCLC cells. We then demonstrated that pro-SFTPB suppresses the formation of the ADRM1/hRpn2/UCH37 complex by binding to ADRM1, which inhibits PGK1 deubiquitination, thus accelerating ubiquitin-mediated PGK1 degradation. In summary, our findings indicate that low expression of pro-SFTPB in primary NSCLC compared to their adjacent tissue has potential as a predictor of recurrence and poor prognosis in early-stage NSCLC. Mechanistically, downregulation of pro-SFTPB attenuates inhibition of ADRM1-deubiquitinated PGK1, resulting in elevated levels of PGK1 protein; this activates the Akt pathway, ultimately leading to the progression of early-stage NSCLC.

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出版当年[2023]版:
大类 | 1 区 医学
小类 | 2 区 血液学 2 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 2 区 血液学 2 区 肿瘤学
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出版当年[2023]版:
Q1 HEMATOLOGY Q1 ONCOLOGY
最新[2023]版:
Q1 HEMATOLOGY Q1 ONCOLOGY

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第一作者机构: [1]Chongqing Univ, Sch Med, Chongqing 400030, Peoples R China [2]Army Med Univ, Daping Hosp, Canc Ctr, Chongqing 400042, Peoples R China
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