PLOD1 promotes cell growth and aerobic glycolysis by regulating the SOX9/PI3K/Akt/mTOR signaling pathway in gastric cancer

Background: Evidences has showed that procollagen-lysine 2-oxoglutarate 5-dioxygenase 1 (PLOD1) participated in the many cancers' progression, such as bladder cancer and osteosarcoma. However, its role in gastric cancer (GC) remains elusive. The study, was aimed to investigate the role and of PLOD1 in GC progression and the underlying mechanism. Methods: MTT, Edu and colony formation assays were applied to detect cell viability and clonal expansion ability. TUNEL was used for cell apoptosis detection. Glucose uptake, lactate production, ATP contents, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) levels were used to reflect aerobic glycolysis level in GC cells. Results: The expression of PLOD1 in GC tissues and cells was higher than that in GES-1 cells. Overexpression of PLOD1 induced a significant enhancement in cell viability and increased glucose uptake, lactate production, ATP contents and ECAR, but decreased cell apoptosis and OCR level in AGS and HGC-27 cells. Knockdown of PLOD1 caused opposite results. In mechanism, the expression of PLOD1 in GC tissues was positively associated with SOX9, HK2 and LDHA levels, and overexpression of PLOD1 increased SOX9, p-Akt/Akt and p-mTOR/mTOR levels. Additionally, overexpression of SOX9 abolished PLOD1 downregulation-mediated inhibition on cell viability and aerobic glycolysis, promotion on cell apoptosis. Moreover, PLOD1 downregulation inhibited tumor formation in vivo. Conclusion: This study showed that PLOD1can promote cell growth and aerobic glycolysis through activating the SOX9/PI3K/Akt/mTOR signaling.