dc.contributor.author | Dongqing Wang | |
dc.contributor.author | Lian Song | |
dc.contributor.author | Hui Shi | |
dc.contributor.author | Xuewen Xu | |
dc.contributor.author | Aihua Gong | |
dc.contributor.author | Hongbo Chen | |
dc.contributor.author | Tao You | |
dc.contributor.author | Haitao Zhu | |
dc.contributor.author | Xin Fan | |
dc.contributor.author | Fang Cheng | |
dc.contributor.author | Yanfang Liu | |
dc.contributor.author | Lirong Zhang | |
dc.date.accessioned | 2022-10-28T13:52:01Z | |
dc.date.available | 2022-10-28T13:52:01Z | |
dc.identifier.uri | https://www.utupub.fi/handle/10024/167934 | |
dc.description.abstract | <p>Differentiated cancer cells reacquiring stem cell traits following radiotherapy may enrich cancer stem cells and accelerate tumor recurrence and metastasis. We are interested in the mechanistic role of dying cells-derived HMGB1 in CD133− pancreatic cancer cells dedifferentiation following radiotherapy. We firstly confirmed that X-ray irradiation induced differentiation of CD133− pancreatic cancer cells, from either sorted from patient samples or established cell lines, into cancer stem-like cells (iCSCs). Using an in vitro coculture model, X-ray irradiation induced dying cells to release HMGB1, which further promoted CD133− pancreatic cancer cells regaining stem cell traits, such as higher sphere forming ability and expressed higher level of stemness-related genes and proteins. Inhibiting the expression and activity of HMGB1 attenuated the dedifferentiation stimulating effect of irradiated, dying cells on C133− pancreatic cancer cells in vitro and in PDX models. Mechanistically, HMGB1 binding with TLR2 receptor functions in a paracrine manner to affect CD133− pancreatic cancer cells dedifferentiation via activating Hippo-YAP pathway and HIF-1α expression in oxygen independent manner in vitro and in vivo. We conclude that X-ray irradiation induces CD133− pancreatic cancer cell dedifferentiation into a CSC phenotype, and inhibiting HMGB1 may be a strategy to prevent CSC enrichment and further pancreatic carcinoma relapse.<br /></p> | |
dc.language.iso | en | |
dc.publisher | Nature Publishing Group | |
dc.title | Dedifferentiation process driven by radiotherapy-induced HMGB1/TLR2/YAP/HIF-1α signaling enhances pancreatic cancer stemness | |
dc.identifier.urn | URN:NBN:fi-fe2021042823978 | |
dc.relation.volume | 10 | |
dc.contributor.organization | fi=biotiedekeskuksen yhteiset|en=Biotiedekeskuksen yhteiset| | |
dc.contributor.organization-code | 2609200 | |
dc.converis.publication-id | 43310115 | |
dc.converis.url | https://research.utu.fi/converis/portal/Publication/43310115 | |
dc.identifier.eissn | 2041-4889 | |
dc.identifier.jour-issn | 2041-4889 | |
dc.okm.affiliatedauthor | Cheng, Fang | |
dc.okm.discipline | 3111 Biomedicine | en_GB |
dc.okm.discipline | 3111 Biolääketieteet | fi_FI |
dc.okm.discipline | 1182 Biokemia, solu- ja molekyylibiologia | fi_FI |
dc.okm.discipline | 1182 Biochemistry, cell and molecular biology | en_GB |
dc.okm.internationalcopublication | international co-publication | |
dc.okm.internationality | International publication | |
dc.okm.type | Journal article | |
dc.publisher.country | United Kingdom | en_GB |
dc.publisher.country | Britannia | fi_FI |
dc.publisher.country-code | GB | |
dc.relation.doi | 10.1038/s41419-019-1956-8 | |
dc.relation.ispartofjournal | Cell Death and Disease | |
dc.relation.issue | 10 | |
dc.year.issued | 2019 | |