HIF-1α Promotes the Confined Migration of Gastric Cancer Cells by Modulating Phosphatidylcholine Metabolism

Confined migration (CM) is a key step in the process of cancer cell metastasis. However, the molecular mechanisms underlying CM in gastric cancer (GC) remain unclear. Here, we found that CM-GC cells had remarkable metastatic and antiapoptotic capacities. Moreover, we observed that HIF-1α was highly expressed in CM-GC cells. HIF-1α knockdown reversed the enhanced metastatic and antiapoptotic capacities of CM-GC cells in vitro and in vivo. Mechanistically, HIF-1α enhanced the metastatic and antiapoptotic capacities of CM-GC cells through phosphatidylcholine (PC) synthesis. Importantly, the addition of L-α-phosphatidylcholine (L-α-PC), a natural PC, markedly increased the metastatic and antiapoptotic capacities of GC cells, similar to CM GC cells. In addition, we observed that increased HIF-1α protein expression was positively correlated with the expression of CEPT1, a key enzyme of PC synthesis, in GC tissue samples. Furthermore, high expression of HIF-1α and CEPT1 in GC tissues predicted poor prognosis in patients with GC. Overall, our study supports the crucial role of HIF-1α in the CM of GC cells and provides novel therapeutic targets and strategies for metastatic GC.