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G protein-coupled receptor 54 (GPR54) plays a role in cancer development by interacting with its endogenous ligand kisspeptin encoded by the\n                    <jats:italic>KISS1<\/jats:italic>\n                    gene. However, the role of GPR54 in NSCLC development is not yet fully understood. Here, we demonstrate that GPR54 regulates NSCLC development via dopa decarboxylase (DDC). A mutant\n                    <jats:italic>Kras<\/jats:italic>\n                    -driven mouse lung cancer model revealed that adenoviral\n                    <jats:italic>CMV-Cre<\/jats:italic>\n                    -mediated\n                    <jats:italic>Gpr54<\/jats:italic>\n                    deletion attenuated NSCLC development. Both\n                    <jats:italic>Gpr54<\/jats:italic>\n                    deletion in mouse NSCLC tissues and\n                    <jats:italic>GPR54<\/jats:italic>\n                    knockdown in human NSCLC cell lines caused apoptotic cell death. In addition, GPR54 regulation of NSCLC cell proliferation involves both the G\u03b1\n                    <jats:sub>q\/11<\/jats:sub>\n                    \/AKT and \u03b2-arrestin\/ERK signaling pathways. RNA sequencing revealed that\n                    <jats:italic>Gpr54<\/jats:italic>\n                    deletion altered a gene set related to glycolysis and genotype-dependently regulated\n                    <jats:italic>Ddc<\/jats:italic>\n                    gene expression. Moreover, the regulation of glycolysis and\n                    <jats:italic>DDC<\/jats:italic>\n                    expression by GPR54 was dependent on the G\u03b1\n                    <jats:sub>q\/11<\/jats:sub>\n                    \/PI3K\/AKT\/mTOR signaling pathway. Phosphoprotein arrays further revealed that DDC regulated NF-\u03baB phosphorylation in NSCLC cells. Consistently, DDC regulated both NSCLC cell proliferation in vitro and tumor growth in vivo. Overall, our findings suggest that GPR54 could be a diagnostic marker for NSCLC and that therapeutics targeting GPR54 signaling may be useful for treating NSCLC.\n                  <\/jats:p>","DOI":"10.1038\/s41392-026-02591-x","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T06:03:16Z","timestamp":1772431396000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GPR54 regulates non-small cell lung cancer development via dopa decarboxylase"],"prefix":"10.1038","volume":"11","author":[{"given":"Hyun-Ha","family":"Hwang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seo Yeon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanhee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Yoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Gyu","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Gook","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"2591_CR1","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/s41392-025-02243-6","volume":"10","author":"Q Huang","year":"2025","unstructured":"Huang, Q. et al. 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