Methylation of NRN1 is a novel synthetic lethal marker of PI3K‐Akt‐mTOR and ATR inhibitors in esophageal cancer

Autor: James G. Herman, Wushuang Du, Lidong Wang, Shunchang Jiao, Aiai Gao, Lirong Zhang, Mingzhou Guo
Rok vydání: 2021
Předmět:
Genetics
Genomics and Proteomics
Male
0301 basic medicine
Cancer Research
DNA Repair
Esophageal Neoplasms
Cell
Apoptosis
Ataxia Telangiectasia Mutated Proteins
Mice
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Cell Movement
DNA damage repair
ATR inhibitor
Promoter Regions
Genetic
PI3K signaling
Phosphoinositide-3 Kinase Inhibitors
Aged
80 and over
DNA methylation
Chemistry
TOR Serine-Threonine Kinases
Age Factors
Wnt signaling pathway
General Medicine
Methylation
Middle Aged
Esophageal cancer
Prognosis
Tumor Burden
medicine.anatomical_structure
Oncology
Pyrazines
030220 oncology & carcinogenesis
Heterografts
Original Article
Female
Esophageal Squamous Cell Carcinoma
Adult
Alcohol Drinking
DNA repair
NRN1
Mice
Nude
GPI-Linked Proteins
03 medical and health sciences
Cell Line
Tumor
Biomarkers
Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
PI3K/AKT/mTOR pathway
Aged
Cell Proliferation
Cell growth
Neuropeptides
Original Articles
medicine.disease
030104 developmental biology
Cancer research
Pyrazoles
Proto-Oncogene Proteins c-akt
Neoplasm Transplantation
DNA Damage
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
DOI: 10.1111/cas.14917
Popis: Wnt, PI3K‐Akt‐mTOR, and NF‐κB pathways were reported to be involved in DNA damage repair (DDR). DDR‐deficient cancers become critically dependent on backup DNA repair pathways. Neuritin 1 (NRN1) is reported to be involved in PI3K‐Akt‐mTOR, and its role in DDR remains unclear. Methylation‐specific PCR, siRNA, flow cytometry, esophageal cancer cell lines, and xenograft mouse models were used to examine the role of NRN1 in esophageal cancer. The expression of NRN1 is frequently repressed by promoter region methylation in human esophageal cancer cells. NRN1 was methylated in 50.4% (510/1012) of primary esophageal cancer samples. NRN1 methylation is associated significantly with age (P
The combination of NVP‐BEZ235 and VE‐822 increased cytotoxicity in NRN1 methylated esophageal cancer cells. Methylation of NRN1 is a novel synthetic lethal marker for PI3K‐Akt‐mTOR and ATR inhibitors in human esophageal cancer.
Databáze: OpenAIRE
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