{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:26:27Z","timestamp":1790727987443,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&amp;D Program of China","award":["2017YFA0506500"],"award-info":[{"award-number":["2017YFA0506500"]}]},{"name":"National Key R&amp;D Program of China","award":["PKU2019LCXQ017"],"award-info":[{"award-number":["PKU2019LCXQ017"]}]},{"name":"National Key R&amp;D Program of China","award":["81972568"],"award-info":[{"award-number":["81972568"]}]},{"name":"National Key R&amp;D Program of China","award":["81802245"],"award-info":[{"award-number":["81802245"]}]},{"name":"Clinical Medicine Plus X-Young Scholars Project of Peking University","award":["2017YFA0506500"],"award-info":[{"award-number":["2017YFA0506500"]}]},{"name":"Clinical Medicine Plus X-Young Scholars Project of Peking University","award":["PKU2019LCXQ017"],"award-info":[{"award-number":["PKU2019LCXQ017"]}]},{"name":"Clinical Medicine Plus X-Young Scholars Project of Peking University","award":["81972568"],"award-info":[{"award-number":["81972568"]}]},{"name":"Clinical Medicine Plus X-Young Scholars Project of Peking University","award":["81802245"],"award-info":[{"award-number":["81802245"]}]},{"name":"National Natural Science Foundation of China","award":["2017YFA0506500"],"award-info":[{"award-number":["2017YFA0506500"]}]},{"name":"National Natural Science Foundation of China","award":["PKU2019LCXQ017"],"award-info":[{"award-number":["PKU2019LCXQ017"]}]},{"name":"National Natural Science Foundation of China","award":["81972568"],"award-info":[{"award-number":["81972568"]}]},{"name":"National Natural Science Foundation of China","award":["81802245"],"award-info":[{"award-number":["81802245"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Directed cell migration towards a softer environment is called negative durotaxis. The mechanism and pathological relevance of negative durotaxis in tumor progression still requires in-depth investigation. Here, we report that YAP promotes the negative durotaxis of melanoma. We uncovered that the RhoA-myosin II pathway may underlie the YAP enhanced negative durotaxis of melanoma cells. Acral melanoma is the most common subtype of melanoma in non-Caucasians and tends to develop in a stress-bearing area. We report that acral melanoma patients exhibit YAP amplification and increased YAP activity. We detected a decreasing stiffness gradient from the tumor to the surrounding area in the acral melanoma microenvironment. We further identified that this stiffness gradient could facilitate the negative durotaxis of melanoma cells. Our study advanced the understanding of mechanical force and YAP in acral melanoma and we proposed negative durotaxis as a new mechanism for melanoma dissemination.<\/jats:p>","DOI":"10.3390\/cells11223543","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T02:07:48Z","timestamp":1668046068000},"page":"3543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["YAP Activation in Promoting Negative Durotaxis and Acral Melanoma Progression"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1260-2725","authenticated-orcid":false,"given":"Yuxing","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China"},{"name":"Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital & Institute, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yi","sequence":"additional","affiliation":[{"name":"Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-9509","authenticated-orcid":false,"given":"Xuan","family":"Meng","sequence":"additional","affiliation":[{"name":"Hepatobiliary Surgery Department, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"},{"name":"Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065000, China"},{"name":"Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Si","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-7884","authenticated-orcid":false,"given":"Congying","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cell.2016.12.039","article-title":"Understanding the Intersections between Metabolism and Cancer 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