Abstract
Nuclear receptor tyrosine kinases (nRTKs) are aberrantly upregulated in many types of cancers, but the regulation of nRTK remains unclear. We previously showed androgen deprivation therapy (ADT) induces nMET in castration-resistant prostate cancer (CRPC) specimens. Through gene expression microarray profiles reanalysis, we identified that nMET signaling requires ARF for CRPC growth in Pten/Trp53 conditional knockout mouse model. Accordingly, aberrant MET/nMET elevation correlates with ARF in human prostate cancer (PCa) specimens. Mechanistically, ARF elevates nMET through binding to MET cytoplasmic domain to stabilize MET. Furthermore, carbon nanodots resensitize cancer cells to MET inhibitors through DNA damage response. The inhibition of phosphorylation by carbon nanodots was identified through binding to phosphate group of phospho-tyrosine via computational calculation and experimental assay. Thus, nMET is essential to precision therapy of MET inhibitor. Our findings reveal for the first time that targeting nMET axis by carbon nanodots can be a novel avenue for overcoming drug resistance in cancers especially prostate cancer.
| Original language | English |
|---|---|
| Journal | Oncogene |
| DOIs | |
| Publication status | Accepted/In press - 1 Jan 2018 |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
Cite this
Nuclear MET requires ARF and is inhibited by carbon nanodots through binding to phospho-tyrosine in prostate cancer. / Xie, Yingqiu; Fan, Haiyan; Lu, Wenfu; Yang, Qing; Nurkesh, Ayan; Yeleussizov, Tleubek; Maipas, Aisulu; Lu, Jiang; Manarbek, Limara; Chen, Zhenbang; Benassi, Enrico.
In: Oncogene, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nuclear MET requires ARF and is inhibited by carbon nanodots through binding to phospho-tyrosine in prostate cancer
AU - Xie, Yingqiu
AU - Fan, Haiyan
AU - Lu, Wenfu
AU - Yang, Qing
AU - Nurkesh, Ayan
AU - Yeleussizov, Tleubek
AU - Maipas, Aisulu
AU - Lu, Jiang
AU - Manarbek, Limara
AU - Chen, Zhenbang
AU - Benassi, Enrico
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Nuclear receptor tyrosine kinases (nRTKs) are aberrantly upregulated in many types of cancers, but the regulation of nRTK remains unclear. We previously showed androgen deprivation therapy (ADT) induces nMET in castration-resistant prostate cancer (CRPC) specimens. Through gene expression microarray profiles reanalysis, we identified that nMET signaling requires ARF for CRPC growth in Pten/Trp53 conditional knockout mouse model. Accordingly, aberrant MET/nMET elevation correlates with ARF in human prostate cancer (PCa) specimens. Mechanistically, ARF elevates nMET through binding to MET cytoplasmic domain to stabilize MET. Furthermore, carbon nanodots resensitize cancer cells to MET inhibitors through DNA damage response. The inhibition of phosphorylation by carbon nanodots was identified through binding to phosphate group of phospho-tyrosine via computational calculation and experimental assay. Thus, nMET is essential to precision therapy of MET inhibitor. Our findings reveal for the first time that targeting nMET axis by carbon nanodots can be a novel avenue for overcoming drug resistance in cancers especially prostate cancer.
AB - Nuclear receptor tyrosine kinases (nRTKs) are aberrantly upregulated in many types of cancers, but the regulation of nRTK remains unclear. We previously showed androgen deprivation therapy (ADT) induces nMET in castration-resistant prostate cancer (CRPC) specimens. Through gene expression microarray profiles reanalysis, we identified that nMET signaling requires ARF for CRPC growth in Pten/Trp53 conditional knockout mouse model. Accordingly, aberrant MET/nMET elevation correlates with ARF in human prostate cancer (PCa) specimens. Mechanistically, ARF elevates nMET through binding to MET cytoplasmic domain to stabilize MET. Furthermore, carbon nanodots resensitize cancer cells to MET inhibitors through DNA damage response. The inhibition of phosphorylation by carbon nanodots was identified through binding to phosphate group of phospho-tyrosine via computational calculation and experimental assay. Thus, nMET is essential to precision therapy of MET inhibitor. Our findings reveal for the first time that targeting nMET axis by carbon nanodots can be a novel avenue for overcoming drug resistance in cancers especially prostate cancer.
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U2 - 10.1038/s41388-018-0608-2
DO - 10.1038/s41388-018-0608-2
M3 - Article
JO - Oncogene
JF - Oncogene
SN - 0950-9232
ER -