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

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. 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. 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. 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.