biostudies-literatureYu HJapan Society for the Promotion of Science3013-3025https://www.ebi.ac.uk/biostudies/studies/S-EPMC11462976biostudies-literatureUnknown115(9)RECK has been described to modulate extracellular matrix components through negative regulation of MMP activities. Recently, RECK was demonstrated to bind to an orphan G protein-coupled receptor GPR124 to mediate WNT7 signaling in nontumor contexts. Here, we attempted to clarify the role of RECK in driving WNT signaling in cancer cells. RECK and GPR124 formed a complex in 293T cells, and when both were expressed, WNT signaling was significantly enhanced in a WNT7-dependent manner. This cooperation was abolished when RECK mutants unable to bind to GPR124 were transduced. RECK stimulated the growth of KRAS-mutated pancreatic ductal adenocarcinoma (PDAC) cells with increased sensitivity to WNT inhibitor in a GPR124-dependent manner. A gastric cancer cell line SH10TC endogenously expresses botCancer scienceRECK/GPR124-driven WNT signaling in pancreatic and gastric cancer cells.PMC1146297619K2255520H03509Takegami YKohno SNakayama JTakahashi CZhang YVoon DCHussein NHYu HfalseRECK/GPR124-driven WNT signaling in pancreatic and gastric cancer cells.RECK has been described to modulate extracellular matrix components through negative regulation of MMP activities. Recently, RECK was demonstrated to bind to an orphan G protein-coupled receptor GPR124 to mediate WNT7 signaling in nontumor contexts. Here, we attempted to clarify the role of RECK in driving WNT signaling in cancer cells. RECK and GPR124 formed a complex in 293T cells, and when both were expressed, WNT signaling was significantly enhanced in a WNT7-dependent manner. This cooperation was abolished when RECK mutants unable to bind to GPR124 were transduced. RECK stimulated the growth of KRAS-mutated pancreatic ductal adenocarcinoma (PDAC) cells with increased sensitivity to WNT inhibitor in a GPR124-dependent manner. A gastric cancer cell line SH10TC endogenously expresses bot2024-01-01T00:00:00Z2024 Sep2026-07-14T19:40:35.55Z2025-04-19T19:25:22.5ZS-EPMC114629763892374110.1111/cas.16258