OncoTargets and Therapy (Feb 2021)

Loss of DAB2IP Contributes to Cell Proliferation and Cisplatin Resistance in Gastric Cancer

  • Wang G,
  • Wang X,
  • Han M,
  • Wang X

Journal volume & issue
Vol. Volume 14
pp. 979 – 988

Abstract

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Guannan Wang,* Xu Wang,* Meng Han, Xiaoming Wang Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoming WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, No. 2 Zheshan West Road, Jinghu District, Wuhu, 241000, Anhui Province, People’s Republic of ChinaEmail [email protected]: Resistance to chemotherapeutic drugs, such as cisplatin, has been one of the major problems adversely affecting the clinical prognosis of patients with gastric cancer (GC). Disabled Homolog 2-Interacting Protein (DAB2IP) status is one of the major factors involved in sensitivity to chemotherapy in multiple cancer types. In the present study, we aimed to investigate the potential roles of DAB2IP in GC cell proliferation and cisplatin resistance.Materials and Methods: DAB2IP expression was detected in human GC tissues using immunohistochemistry (IHC). The role of DAB2IP in regulating GC cell proliferation and cisplatin resistance was explored by genetic manipulation. Western blot analysis was used to determine the molecular signaling to explain the mechanism of the observed DAB2IP effects in GC.Results: DAB2IP expression was downregulated in human GC tissues and low DAB2IP expression predicted poor prognosis. Moreover, our data provided evidence that DAB2IP upregulation impaired cell proliferation property and sensitized GC cells to cisplatin while DAB2IP depletion possessed the opposite effects. Mechanistically, we showed that DAB2IP could inhibit the phosphorylation and activation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK), and the enhanced proliferation ability induced by DAB2IP knockdown was greatly impaired after incubation with AKT or ERK inhibitor.Conclusion: DAB2IP modulates GC cell proliferation and sensitivity to cisplatin potentially via regulation of AKT and ERK signaling pathway, indicating that DAB2IP may serve as a potential prognostic biomarker and therapeutic target for treatment of GC.Keywords: DAB2IP, proliferation, chemoresistance, gastric cancer

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