Journal article
Pten-NOLC1 fusion promotes cancers involving MET and EGFR signalings
Oncogene, Vol.40(6), pp.1064-1076
02/2021
DOI: 10.1038/s41388-020-01582-8
PMCID: PMC7880894
PMID: 33323972
Abstract
Inactivation of Pten gene through deletions and mutations leading to excessive pro-growth signaling pathway activations frequently occurs in cancers. Here, we report a Pten derived pro-cancer growth gene fusion Pten-NOLC1 originated from a chr10 genome rearrangement and identified through a transcriptome sequencing analysis of human cancers. Pten-NOLC1 fusion is present in primary human cancer samples and cancer cell lines from different organs. The product of Pten-NOLC1 is a nuclear protein that interacts and activates promoters of EGFR, c-MET, and their signaling molecules. Pten-NOLC1 promotes cancer proliferation, growth, invasion, and metastasis, and reduces the survival of animals xenografted with Pten-NOLC1-expressing cancer cells. Genomic disruption of Pten-NOLC1 induces cancer cell death, while genomic integration of this fusion gene into the liver coupled with somatic Pten deletion produces spontaneous liver cancers in mice. Our studies indicate that Pten-NOLC1 gene fusion is a driver for human cancers.
Details
- Title: Subtitle
- Pten-NOLC1 fusion promotes cancers involving MET and EGFR signalings
- Creators
- Jian-Hua Luo - University of Pittsburgh School of MedicineSilvia Liu - University of PittsburghJunyan Tao - University of PittsburghBao-Guo Ren - University of Pittsburgh School of MedicineKatherine Luo - Columbia UniversityZhang-Hui Chen - University of Pittsburgh School of MedicineMichael Nalesnik - University of PittsburghKathleen Cieply - University of PittsburghTianzhou Ma - University of PittsburghShi-Yuan Cheng - Northwestern MedicineQi Chen - University of KansasGeorge K Michalopoulos - University of PittsburghJoel B Nelson - University of PittsburghRohit Bhargava - University of PittsburghJun Zhang - University of IowaDeqin Ma - University of IowaDavid Jarrard - University of Wisconsin–MadisonArjun Pennathur - University of PittsburghJames D Luketich - University of PittsburghDonald B DeFranco - University of PittsburghSatdarshan Paul Monga - University of PittsburghGeorge Tseng - Columbia UniversityYan-Ping Yu - University of Pittsburgh School of Medicine
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.40(6), pp.1064-1076
- DOI
- 10.1038/s41388-020-01582-8
- PMID
- 33323972
- PMCID
- PMC7880894
- NLM abbreviation
- Oncogene
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Grant note
- R56 CA229262 / NCI NIH HHS R01 CA098249 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 02/2021
- Academic Unit
- Pathology; Internal Medicine
- Record Identifier
- 9984186576202771
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