Nuclear MET requires ARF and is inhibited by carbon nanodots through binding to phospho-tyrosine in prostate cancer

Yingqiu Xie, Haiyan Fan, Wenfu Lu, Qing Yang, Ayan Nurkesh, Tleubek Yeleussizov, Aisulu Maipas, Jiang Lu, Limara Manarbek, Zhenbang Chen, Enrico Benassi

Research output: Contribution to journalArticle

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 languageEnglish
JournalOncogene
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Tyrosine
Prostatic Neoplasms
Carbon
Castration
Cytoplasmic and Nuclear Receptors
Protein-Tyrosine Kinases
Transcriptome
Drug Resistance
Knockout Mice
Androgens
DNA Damage
Neoplasms
Phosphates
Phosphorylation
Therapeutics
Growth

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 journalArticle

Xie, Yingqiu ; Fan, Haiyan ; Lu, Wenfu ; Yang, Qing ; Nurkesh, Ayan ; Yeleussizov, Tleubek ; Maipas, Aisulu ; Lu, Jiang ; Manarbek, Limara ; Chen, Zhenbang ; Benassi, Enrico. / Nuclear MET requires ARF and is inhibited by carbon nanodots through binding to phospho-tyrosine in prostate cancer. In: Oncogene. 2018.
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AU - Maipas, Aisulu

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