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Sökning: WFRF:(Sund Fredrik) > (2020-2024) > Targeting collagen ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003716naa a2200613 4500
001oai:gup.ub.gu.se/332911
003SwePub
008240528s2023 | |||||||||||000 ||eng|
024a https://gup.ub.gu.se/publication/3329112 URI
024a https://doi.org/10.1172/jci1591812 DOI
040 a (SwePub)gu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Devarajan, R.4 aut
2451 0a Targeting collagen XVIII improves the efficiency of ErbB inhibitors in breast cancer models
264 1c 2023
520 a 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 alpha 6-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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng
653 a stem-cells
653 a drug-resistance
653 a mechanisms
653 a expression
653 a trastuzumab
653 a metastasis
653 a receptors
653 a integrins
653 a survival
653 a isoforms
653 a Research & Experimental Medicine
700a Izzi, V.4 aut
700a Peltoketo, H.4 aut
700a Rask, G.4 aut
700a Kauppila, S.4 aut
700a Väisänen, M. R.4 aut
700a Ruotsalainen, H.4 aut
700a Martinez-Nieto, G.4 aut
700a Karppinen, S. M.4 aut
700a Väisänen, T.4 aut
700a Kaur, I.4 aut
700a Koivunen, J.4 aut
700a Sasaki, T.4 aut
700a Winqvist, R.4 aut
700a Manninen, A.4 aut
700a Wärnberg, Fredriku Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery4 aut0 (Swepub:gu)xwarnf
700a Sund, M.4 aut
700a Pihlajaniemi, T.4 aut
700a Heljasvaara, R.4 aut
710a Göteborgs universitetb Institutionen för kliniska vetenskaper, Avdelningen för kirurgi4 org
773t Journal of Clinical Investigationg 133:18q 133:18x 0021-9738
8564 8u https://gup.ub.gu.se/publication/332911
8564 8u https://doi.org/10.1172/jci159181

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