COL1A1 modulates apatinib sensitivity through promoting glycolysis and angiogenesis in gastric cancer cells.

BACKGROUND: Our previous bioinformatic study identified Collagen type I alpha 1 chain (COL1A1) as a candidate regulator associated with gastric cancer (GC) progression and response to anti-angiogenic therapy. However, whether COL1A1 influences the sensitivity of GC cells to apatinib and the underlying mechanisms remains unclear. METHODS: Multiple bioinformatics platforms were used to investigate the correlation between COL1A1 expression and GC progression and prognosis. Gain- and loss-of-function assays were conducted in GC cell lines to validate the regulatory role of COL1A1 in apatinib sensitivity. Functional validation included a series of in vitro and in vivo studies. Protein expression profiling was further performed to quantify key proteins involved in glycolytic and angiogenic signaling pathways. RESULTS: High COL1A1 expression was associated with tumor progression and poor prognosis in GC patients. Knockdown of COL1A1 enhanced the sensitivity of MKN-74 cells to apatinib and weakened their proliferative, migratory, invasive, and colony-forming abilities in vitro, as well as tumor growth and metastasis in vivo. Overexpression of COL1A1 in SNU-1 cells had the opposite effects. Mechanistically, COL1A1 modulated glycolytic reprogramming and profoundly affected the angiogenic potential of GC cells, uncovering its role in driving therapeutic evasion. CONCLUSION: COL1A1 may contribute to reduced apatinib sensitivity in GC cells, at least partly by enhancing glycolytic metabolism and angiogenic activity. These findings suggest that COL1A1 is a potential regulator worthy of further investigation for improving the therapeutic response to apatinib in GC.