Aldolase A promotes cell proliferation and cisplatin resistance via the EGFR pathway in gastric cancer.

Background: Gastric cancer is the third leading cause of cancer-related mortality worldwide, and the 5-year survival rate remains poor, globally. Overexpression of Aldolase A (ALDOA) has been linked to tumor cell proliferation and metastasis in numerous cancer types, including pancreatic, colorectal, hepatocellular carcinoma, and lung cancer. Although the significance of ALDOA as a potential biomarker in GC prognosis has been reported, its potential role and possible mechanism of ALDOA in GC cell sensitivity to chemotherapy remains to be elucidated.

Methods: The GEPIA platform and clinical samples were used to investigate ALDOA expression in GC tumors and neighboring normal tissues. The CCK8 and colony formation tests were used to examine whether ALDOA increased GC cell proliferation and decreased resistance to the chemotherapy drug cisplatin. Furthermore, the underlying molecular mechanisms were elucidated.

Results: Overexpression of ADOLA was seen in GC tumors and GC cells. Prognostic markers, i.e., invasion depth, tumor size, and metastasis of lymph node were all negatively impacted by ADOLA overexpression. Following ADOLA knockdown, proliferation of AGS cells was decreased and drug resistance was reduced. Conversely, ADOLA overexpression exhibited an inverse effect in MKN45 cells. ALDOA knockdown dramatically slowed the development of GC tumors in experiments. Mechanistically, ADOLA regulated the activity of epidermal growth factor receptor (EGFR), its downstream molecue the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) signaling pathway in GC cells. Moreover, in the absence of EGFR, ALDOA overexpression had no effect on GC cell growth.

Conclusion: In the EGFR signaling pathway, ADOLA boosted the proliferation and cisplatin resistance of GC cells, making it a viable GC therapeutic target.