Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/191038
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Alvarez Varela, Adrián | - |
dc.contributor.author | Novellasdemunt, Laura | - |
dc.contributor.author | Barriga, Francisco M. | - |
dc.contributor.author | Hernando Momblona, Xavier | - |
dc.contributor.author | Cañellas Socias, Adrià | - |
dc.contributor.author | Cano Crespo, Sara | - |
dc.contributor.author | Sevillano, Marta | - |
dc.contributor.author | Cortina, Carme | - |
dc.contributor.author | Stork, Diana | - |
dc.contributor.author | Morral, Clara | - |
dc.contributor.author | Turon, Gemma | - |
dc.contributor.author | Slebe, Felipe | - |
dc.contributor.author | Jimenez Gracia, Laura | - |
dc.contributor.author | Caratu, Ginevra | - |
dc.contributor.author | Jung, Peter | - |
dc.contributor.author | Stassi, Giorgio | - |
dc.contributor.author | Heyn, Holger | - |
dc.contributor.author | Tauriello, Daniele V. F. | - |
dc.contributor.author | Mateo, Lidia | - |
dc.contributor.author | Tejpar, Sabine | - |
dc.contributor.author | Sancho, Elena | - |
dc.contributor.author | Attolini, Camille Stephan-Otto | - |
dc.contributor.author | Batlle, Eduard | - |
dc.date.accessioned | 2022-11-24T09:58:15Z | - |
dc.date.available | 2022-12-30T06:10:28Z | - |
dc.date.issued | 2022-06-30 | - |
dc.identifier.issn | 2662-1347 | - |
dc.identifier.issn | 6554054 | - |
dc.identifier.uri | http://hdl.handle.net/2445/191038 | - |
dc.description.abstract | Colorectal cancer (CRC) patient-derived organoids predict responses to chemotherapy. Here we used them to investigate relapse after treatment. Patient-derived organoids expand from highly proliferative LGR5(+) tumor cells; however, we discovered that lack of optimal growth conditions specifies a latent LGR5(+) cell state. This cell population expressed the gene MEX3A, is chemoresistant and regenerated the organoid culture after treatment. In CRC mouse models, Mex3a(+) cells contributed marginally to metastatic outgrowth; however, after chemotherapy, Mex3a(+) cells produced large cell clones that regenerated the disease. Lineage-tracing analysis showed that persister Mex3a(+) cells downregulate the WNT/stem cell gene program immediately after chemotherapy and adopt a transient state reminiscent to that of YAP(+) fetal intestinal progenitors. In contrast, Mex3a-deficient cells differentiated toward a goblet cell-like phenotype and were unable to resist chemotherapy. Our findings reveal that adaptation of cancer stem cells to suboptimal niche environments protects them from chemotherapy and identify a candidate cell of origin of relapse after treatment in CRC. Batlle and colleagues report that after chemotherapy, Mex3a(+) colorectal cancer cells represent drug-tolerant persister cells that lead to recurrence by downregulating the WNT-Lgr5(+) stem cell program and adopting a transient regenerative state. | ca |
dc.format.extent | 64 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | ca |
dc.publisher | Springer Nature | ca |
dc.relation.isformatof | Postprint del document publicat a: https://doi.org/10.1038/s43018-022-00402-0 | - |
dc.relation.ispartof | Nature Cancer, 2022, num. 3, p. 1052–1070 | - |
dc.relation.uri | https://doi.org/10.1038/s43018-022-00402-0 | - |
dc.rights | (c) Alvarez Varela, Adrián et al, 2022 | - |
dc.source | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) | - |
dc.subject.classification | Càncer colorectal | - |
dc.subject.classification | Quimioteràpia del càncer | - |
dc.subject.other | Colorectal cancer | - |
dc.subject.other | Cancer chemotherapy | - |
dc.title | Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy | ca |
dc.type | info:eu-repo/semantics/article | ca |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.date.updated | 2022-11-23T10:31:02Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.idimarina | 6554054 | - |
dc.identifier.pmid | 35773527 | - |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
NatCan_Alvarez-Varela_2022.pdf | 13.49 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.