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

Abstract

Objective

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

Disclosure

All authors declare that they have no conflicts of interest.

Additional information

Funding

This study was supported by the Anhui Provincial Central Government's Special Program for Local Science and Technology Development (Grant No. YDZX20183400004899), University Academic (Professional) Top Talents Academic Funding Project (Grant No. gxbjZD17), grants from the First Affiliated Hospital of Wannan Medical College (Grant No. KGF2019703 and KPF2019011), and the Nature and Science Fund from Wannan Medical College, CN (Grant No. WK2019F07).