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Here, we report the first analysis of Palladin expression and its impacts on stem cell\u2010like properties in lung cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tissue microarrays were used to investigate Palladin expression and its association with prognosis. Immunofluorescence (IF), flow fluorescence assay, and Western blot were performed to detect Palladin expression in 6 NSCLC cell lines. Cell phenotypes and drug resistance were evaluated. Xenograft models were constructed to confirm the role of Palladin in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By using the tissue microarrays, Palladin was identified to be highly expressed in the cytoplasm, specifically in the cytomembrane of NSCLC, and its high expression is associated with poor prognosis. Palladin is widely expressed and enriched in the sphere cells. The in vitro and in vivo studies showed that Palladin promoted stem cell\u2010like properties, including cell viability, invasion, migration, self\u2010renewal abilities, taxol resistance, and tumorigenicity. Western blot revealed that Palladin promoted the accumulation of \u03b2\u2010catenin and activated Wnt\/\u03b2\u2010catenin signaling. Tissue microarrays analysis further confirmed the positive correlation between Palladin and \u03b2\u2010catenin. Wnt\/\u03b2\u2010catenin pathway inhibitor blocked the Palladin\u2010induced enhancement of sphere\u2010forming.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Palladin might act as an oncogene by promoting CSCs\u2010like properties and tumorigenicity of NSCLC cells via the Wnt\/\u03b2\u2010catenin signaling pathway. Besides, Palladin was identified to have the potential as a cell surface marker for LCSCs identification. These findings provide a possible target for developing putative agents targeted to LCSCs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5192","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T11:57:27Z","timestamp":1662033447000},"page":"4510-4520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Palladin promotes cancer stem cell\u2010like properties in lung cancer by activating Wnt\/<scp>\u0392\u2010Catenin<\/scp> signaling"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiong","family":"Shu","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Orthopaedics Beijing Research Institute of Orthopaedics and Traumatology, Beijing JiShuiTan Hospital  Beijing P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing P. R. 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