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

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 in CRPC in vivo Arf deficiency 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 phosphory-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.

Date Pit Carbon Dots Induce Acidic Inhibition of Peroxidase and Disrupt DNA Repair in Antibacteria Resistance

“…In summary, we systematically analyzed the C‐dots‐mediated nanozyme, DNA damage, DNA repair, and cell death in both cancer cells and bacteria with novel discovery that the C‐dots induce pH‐mediated nanozyme inhibition, photo‐induced nanozyme activity, destroy of BER‐mediated DNA repair, and kinase‐mediated cell proliferation, which are consistent with our previous hypothesis of MET kinase synergistic DNA damage targeted pathway …”

Generation of particle assemblies mimicking enzymatic activity by processing of herbal food: the case of rhizoma polygonati and other natural ingredients in traditional Chinese medicine

“…In our previous research, carbon nanodots developed from food or herbal food were shown to exhibit PL activity, and their binding to the phosphate group on the protein was identied by molecular spectroscopy and supported by quantum mechanical calculations. 30 Phosphatases, especially tyrosine phosphatase (PTP), have been recognized to suppress cancer cell growth and other oncogenic characteristics by intervening in cell signaling, wherein phosphatase most likely dysregulates the phosphorylation-dephosphorylation balance to disrupt cancer cell signaling. [31][32][33] As a continuation of our previous work, we aim to correlate the nanostructures or their assemblies formed through RP processing with the enzyme-like activities demonstrated in the nal products by means of FT-IR spectroscopy and enzymatic tests combined with quantum mechanical calculations.…”

Nano-evolution and protein-based enzymatic evolution predicts novel types of natural product nanozymes of traditional Chinese medicine: cases of herbzymes of Taishan-Huangjing (Rhizoma polygonati) and Goji (Lycium chinense)

“…(3) Hydrolase of ALP One example of a class of hydrolase is alkaline phosphatase (ALP) (EC 3.1.3.1) which functions as removing of phosphorylation and some types of nanoparticles have been reported to have intrinsic phosphatase activity [11,16]. Recently we discovered natural product derived nanodots or nanoflowers which have the ability to dephosphorylate substrates as ALP-like nanozymes in addition to the chemical synthesis of nanozyme [9,11,17].…”