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dc.contributor.authorKatajisto, Pekka
dc.contributor.authorTammela, Tuomas
dc.contributor.authorCetinbas, Naniye
dc.contributor.authorWu, Katherine
dc.contributor.authorHelenius, Katja Piritta
dc.contributor.authorPark, Yoona K
dc.contributor.authorAzimi, Roxana S.
dc.contributor.authorKerper, Natanya R.
dc.contributor.authorWesselhoeft IV, Robert Alexander
dc.contributor.authorGu, Xin
dc.contributor.authorSchmidt, Leah Marie
dc.contributor.authorCornwall-Brady, Milton R.
dc.contributor.authorYilmaz, Omer
dc.contributor.authorXue, Wen
dc.contributor.authorBhutkar, Arjun
dc.contributor.authorJacks, Tyler E
dc.contributor.authorSanchez-Rivera, Francisco Jav
dc.contributor.authorJoshi, Nik
dc.date.accessioned2018-06-26T14:06:46Z
dc.date.available2018-06-26T14:06:46Z
dc.date.issued2017-05
dc.date.submitted2016-07
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.urihttp://hdl.handle.net/1721.1/116606
dc.description.abstractThe heterogeneity of cellular states in cancer has been linked to drug resistance, cancer progression and the presence of cancer cells with properties of normal tissue stem cells. Secreted Wnt signals maintain stem cells in various epithelial tissues, including in lung development and regeneration. Here we show that mouse and human lung adenocarcinomas display hierarchical features with two distinct subpopulations, one with high Wnt signalling activity and another forming a niche that provides the Wnt ligand. The Wnt responder cells showed increased tumour propagation ability, suggesting that these cells have features of normal tissue stem cells. Genetic perturbation of Wnt production or signalling suppressed tumour progression. Small-molecule inhibitors targeting essential posttranslational modification of Wnt reduced tumour growth and markedly decreased the proliferative potential of lung cancer cells, leading to improved survival of tumour-bearing mice. These results indicate that strategies for disrupting pathways that maintain stem-like and niche cell phenotypes can translate into effective anti-cancer therapies.en_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/NATURE22334en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleA Wnt-producing niche drives proliferative potential and progression in lung adenocarcinomaen_US
dc.typeArticleen_US
dc.identifier.citationTammela, Tuomas et al. “A Wnt-Producing Niche Drives Proliferative Potential and Progression in Lung Adenocarcinoma.” Nature 545, 7654 (May 2017): 355–359 © 2017 Macmillan Publishers Limited, part of Springer Natureen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorTammela, Tuomas
dc.contributor.mitauthorSanchez-Rivera, Francisco Javier
dc.contributor.mitauthorCetinbas, Naniye
dc.contributor.mitauthorWu, Katherine
dc.contributor.mitauthorJoshi, Nikhil
dc.contributor.mitauthorHelenius, Katja Piritta
dc.contributor.mitauthorPark, Yoona K
dc.contributor.mitauthorAzimi, Roxana S.
dc.contributor.mitauthorKerper, Natanya R.
dc.contributor.mitauthorWesselhoeft IV, Robert Alexander
dc.contributor.mitauthorGu, Xin
dc.contributor.mitauthorSchmidt, Leah Marie
dc.contributor.mitauthorCornwall-Brady, Milton R.
dc.contributor.mitauthorYilmaz, Omer
dc.contributor.mitauthorXue, Wen
dc.contributor.mitauthorBhutkar, Arjun
dc.contributor.mitauthorJacks, Tyler E
dc.relation.journalNatureen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-06-25T14:23:04Z
dspace.orderedauthorsTammela, Tuomas; Sanchez-Rivera, Francisco J.; Cetinbas, Naniye Malli; Wu, Katherine; Joshi, Nikhil S.; Helenius, Katja; Park, Yoona; Azimi, Roxana; Kerper, Natanya R.; Wesselhoeft, R. Alexander; Gu, Xin; Schmidt, Leah; Cornwall-Brady, Milton; Yilmaz, Ömer H.; Xue, Wen; Katajisto, Pekka; Bhutkar, Arjun; Jacks, Tyleren_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-3675-6961
dc.identifier.orcidhttps://orcid.org/0000-0002-7045-7837
dc.identifier.orcidhttps://orcid.org/0000-0001-8031-0006
dc.identifier.orcidhttps://orcid.org/0000-0003-4617-8157
dc.identifier.orcidhttps://orcid.org/0000-0002-3393-6927
dc.identifier.orcidhttps://orcid.org/0000-0001-9076-8475
dc.identifier.orcidhttps://orcid.org/0000-0002-7577-4612
dc.identifier.orcidhttps://orcid.org/0000-0001-5785-8911
mit.licensePUBLISHER_POLICYen_US


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