2. Academic Validation
  3. STAMBP promotes lung adenocarcinoma metastasis by regulating the EGFR/MAPK signaling pathway

STAMBP promotes lung adenocarcinoma metastasis by regulating the EGFR/MAPK signaling pathway

  • Neoplasia. 2021 Jun;23(6):607-623. doi: 10.1016/j.neo.2021.05.011.
Hui Xu 1,  Xiaomei Yang 2,  Xiaofeng Xuan 3,  Di Wu 4,  Jieru Zhang 3,  Xinchun Xu 5,  Yuanjie Zhao 6,  Chunping Ma 7,  Dawei Li 8
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China; Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China.
  • 2 Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China; Department of Emergency, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China.
  • 3 Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China; Department of Respiratory & Critical Care Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China.
  • 4 Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China.
  • 5 Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China; Department of Ultrasound, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China.
  • 6 Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China; Department of General Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China.
  • 7 Department of Thoracic Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China. Electronic address: [email protected].
  • 8 Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China; Lead Contact. Electronic address: [email protected].
PMID: 34102455 DOI: 10.1016/j.neo.2021.05.011
Abstract

Tumor metastasis is a leading cause of death in lung adenocarcinoma (LUAD) patients, but the molecular events that regulate metastasis have not been completely elucidated. STAMBP is a deubiquitinating enzyme of the Jab1/MPN metalloenzyme family that regulates the stability of substrates in cells by specifically removing ubiquitin molecules. We found that STAMBP expression was increased in the cytoplasm of tumor cells from LUAD patients. The STAMBP level was closely associated with tumor size, lymph node invasion and neoplasm disease stage. A high STAMBP level predicted poor overall survival and disease-free survival in LUAD patients. STAMBP overexpression promoted cell migration and invasion, whereas STAMBP knockdown attenuated these processes in LUAD cells after epidermal growth factor treatment. Mechanistically, increased STAMBP expression promoted the stabilization of Epidermal growth factor receptor (EGFR), whereas STAMBP knockdown induced the degradation of EGFR. STAMBP may deubiquitinate EGFR by localizing in early endosomes and increase EGFR membrane localization in LUAD cells. The overexpression of STAMBP triggered the activation of MAPK signaling after epidermal growth factor treatment. In contrast, this activation was attenuated in STAMBP knockdown cells. Small molecule inhibitors of EGFR and MAPK signaling pathway may block STAMBP-induced cell mobility and invasion as well as ERK activation in cells. Importantly, STAMBP knockdown suppressed LUAD tumor growth and metastasis by regulating the EGFR-mediated ERK activation in a xenograft mouse model. Our findings identified STAMBP as a novel potential target for LUAD therapy.

Keywords

EGFR; ERK; Lung adenocarcinoma; MAPK; Metastasis; STAMBP.

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