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Targeting collagen ...
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Devarajan, RamanOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine; Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland
(författare)
Targeting collagen XVIII improves the efficiency of ErbB inhibitors in breast cancer models
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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American Society for Clinical Investigation,2023
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:umu-214769
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-214769URI
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https://doi.org/10.1172/JCI159181DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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The tumor extracellular matrix (ECM) critically regulates cancer progression and treatment response. Expression of the basement membrane component collagen XVIII (ColXVIII) is induced in solid tumors, but its involvement in tumorigenesis has remained elusive. We show here that ColXVIII was markedly upregulated in human breast cancer (BC) and was closely associated with a poor prognosis in high-grade BCs. We discovered a role for ColXVIII as a modulator of epidermal growth factor receptor tyrosine kinase (ErbB) signaling and show that it forms a complex with ErbB1 and -2 (also known as EGFR and human epidermal growth factor receptor 2 [HER2]) and α6-integrin to promote cancer cell proliferation in a pathway involving its N-terminal portion and the MAPK/ERK1/2 and PI3K/AKT cascades. Studies using Col18a1 mouse models crossed with the mouse mammary tumor virus-polyoma virus middle T antigen (MMTV-PyMT) mammary carcinogenesis model showed that ColXVIII promoted BC growth and metastasis in a tumor cell-autonomous manner. Moreover, the number of mammary cancer stem cells was significantly reduced in the MMTV-PyMT and human cell models upon ColXVIII inhibition. Finally, ablation of ColXVIII substantially improved the efficacy of ErbB-targeting therapies in both preclinical models. In summary, ColXVIII was found to sustain the stemness properties of BC cells and tumor progression and metastasis through ErbB signaling, suggesting that targeting ColXVIII in the tumor milieu may have important therapeutic potential.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Izzi, ValerioOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Research Unit of Biomedicine, University of Oulu, Oulu, Finland; Finnish Cancer Research Institute, Helsinki, Finland
(författare)
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Peltoketo, HelleviLaboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland
(författare)
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Rask, GunillaUmeå universitet,Patologi(Swepub:umu)guarak02
(författare)
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Kauppila, SailaDepartment of Pathology, Oulu University Hospital and University of Oulu, Oulu, Finland; Northern Finland Laboratory Centre, NordLab, Oulu, Finland
(författare)
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Väisänen, Marja-RiittaDepartment of Pathology, Kainuu Central Hospital, Kajaani, Finland
(författare)
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Ruotsalainen, HeliOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
(författare)
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Martínez-Nieto, GuillermoOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
(författare)
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Karppinen, Sanna-MariaOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
(författare)
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Väisänen, TimoDepartment of Pathology, Oulu University Hospital and University of Oulu, Oulu, Finland
(författare)
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Kaur, InderjeetOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
(författare)
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Koivunen, JussiDepartment of Medical Oncology and Radiotherapy and Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
(författare)
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Sasaki, TakakoDepartment of Pharmacology, Faculty of Medicine, Oita University, Oita, Japan
(författare)
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Winqvist, RobertLaboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit; Biocenter Oulu, University of Oulu, Oulu, Finland; Northern Finland Laboratory Centre, NordLab, Oulu, Finland
(författare)
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Manninen, AkiDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
(författare)
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Wärnberg, FredrikDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
(författare)
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Sund, MalinUmeå universitet,Institutionen för kirurgisk och perioperativ vetenskap,Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland(Swepub:umu)masu0021
(författare)
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Pihlajaniemi, TainaOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
(författare)
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Heljasvaara, RitvaOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
(författare)
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Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine; Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, FinlandOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Research Unit of Biomedicine, University of Oulu, Oulu, Finland; Finnish Cancer Research Institute, Helsinki, Finland
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Clinical Investigation: American Society for Clinical Investigation133:180021-97381558-8238
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Till lärosätets databas
- Av författaren/redakt...
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Devarajan, Raman
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Izzi, Valerio
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Peltoketo, Helle ...
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Rask, Gunilla
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Kauppila, Saila
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Väisänen, Marja- ...
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visa fler...
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Ruotsalainen, He ...
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Martínez-Nieto, ...
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Karppinen, Sanna ...
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Väisänen, Timo
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Kaur, Inderjeet
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Koivunen, Jussi
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Sasaki, Takako
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Winqvist, Robert
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Manninen, Aki
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Wärnberg, Fredri ...
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Sund, Malin
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Pihlajaniemi, Ta ...
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Heljasvaara, Rit ...
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