Meder, Lydia ORCID: 0000-0002-9547-5812, Koenig, Katharina, Dietlein, Felix, Macheleidt, Iris, Florin, Alexandra, Ercanoglu, Meryem S., Rommerscheidt-Fuss, Ursula, Koker, Mirjam, Schoen, Gisela, Odenthal, Margarete, Klein, Florian, Buettner, Reinhard, Schulte, Johannes H., Heukamp, Lukas C. and Ullrich, Roland T. (2018). LIN28B enhanced tumorigenesis in an autochthonous KRAS(G12V)-driven lung carcinoma mouse model. Oncogene, 37 (20). S. 2746 - 2757. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5594

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Abstract

LIN28B is a RNA-binding protein regulating predominantly let-7 microRNAs with essential functions in inflammation, wound healing, embryonic stem cells, and cancer. LIN28B expression is associated with tumor initiation, progression, resistance, and poor outcome in several solid cancers, including lung cancer. However, the functional role of LIN28B, especially in non-small cell lung adenocarcinomas, remains elusive. Here, we investigated the effects of LIN28B expression on lung tumorigenesis using LIN28B transgenic overexpression in an autochthonous KRAS(G12V)-driven mouse model. We found that LIN28B overexpression significantly increased the number of CD44+/CD326+ tumor cells, upregulated VEGF-A and miR-21 and promoted tumor angiogenesis and epithelial-to-mesenchymal transition (EMT) accompanied by enhanced AKT phosphorylation and nuclear translocation of c-MYC. Moreover, LIN28B accelerated tumor initiation and enhanced proliferation which led to a shortened overall survival. In addition, we analyzed lung adenocarcinomas of the Cancer Genome Atlas (TCGA) and found LIN28B expression in 24% of KRAS-mutated cases, which underscore the relevance of our model.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Meder, LydiaUNSPECIFIEDorcid.org/0000-0002-9547-5812UNSPECIFIED
Koenig, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dietlein, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macheleidt, IrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Florin, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ercanoglu, Meryem S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rommerscheidt-Fuss, UrsulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koker, MirjamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoen, GiselaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, Johannes H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heukamp, Lukas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ullrich, Roland T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-187756
DOI: 10.1038/s41388-018-0158-7
Journal or Publication Title: Oncogene
Volume: 37
Number: 20
Page Range: S. 2746 - 2757
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-5594
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EPITHELIAL-MESENCHYMAL TRANSITION; CANCER PATIENTS; K-RAS; MULTIPLE MECHANISMS; CELL-PROLIFERATION; PANCREATIC-CANCER; DOWN-REGULATION; KRAS MUTATIONS; BREAST-CANCER; SELF-RENEWALMultiple languages
Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18775

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