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Moreover, PD\u20101\/PD\u2010L1 blockade reduces the apoptosis and exhaustion of T cells and inhibits the development of malignant tumors. Usnic acid is a dibenzofuran compound originating from <jats:italic>Usnea diffracta<\/jats:italic> Vain and has anti\u2010inflammatory, antifungal, and anticancer activities. However, the molecular mechanism of its antitumor effects has not been fully elucidated. In this work, we first observed that usnic acid decreased the expression of PD\u2010L1 in HeLa cells and enhanced the cytotoxicity of co\u2010cultured T cells toward tumor cells. Usnic acid inhibited PD\u2010L1 protein synthesis by reducing STAT3 and RAS pathways cooperatively. It was subsequently shown that usnic acid induced MiT\/TFE nuclear translocation through the suppression of mTOR signaling pathways, and promoted the biogenesis of lysosomes and the translocation of PD\u2010L1 to the lysosomes for proteolysis. Furthermore, usnic acid inhibited cell proliferation, angiogenesis, migration, and invasion, respectively, by downregulating PD\u2010L1, thereby inhibiting tumor growth. Taken together, our results show that usnic acid is an effective inhibitor of PD\u2010L1 and our study provide novel insights into the mechanism of its anticancer targeted therapy.<\/jats:p>","DOI":"10.1002\/ptr.7103","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T13:42:58Z","timestamp":1620654178000},"page":"3916-3935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Usnic acid suppresses cervical cancer cell proliferation by inhibiting <scp>PD\u2010L1<\/scp> expression and enhancing T\u2010lymphocyte tumor\u2010killing activity"],"prefix":"10.1002","volume":"35","author":[{"given":"Tong Xin","family":"Sun","sequence":"first","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xing","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MyongHak","family":"Ri","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Hua","family":"Jin","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian Xun","family":"Piao","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Lan","family":"Jin","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Xiang","family":"Zuo","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Ma","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6998-2602","authenticated-orcid":false,"given":"Xuejun","family":"Jin","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center College of Pharmacy, Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20748"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30482-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-2606"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5557"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.03.023"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200694"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23643"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.10.004"},{"key":"e_1_2_10_10_1","first-page":"291","volume-title":"Kang Ai Zhong Yao","author":"Chang M. 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