Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance.

BACKGROUND: Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. METHOD: We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. RESULTS: We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. CONCLUSION: Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy.

Application of Electrically Charged Carbon Nanodots@glass in DNA and Cell Engineering.

Water-soluble carbon nanodots (C-dots) prepared from food, or food wastes generally have a size below 10 nm and emit fluorescence upon the UV radiation with environmental safe specialty. These features of C-dots have been taken advantages in the areas of drug delivery as well as the inhibition of cancer cell growth as green carbon nanoparticles. The electrically physical, chemical characteristics and the mechanisms of their various applications, however, remain unclear. In the present work, we were attempted to develop the C-dots that carry charges which can be later embedded in the glass beads to achieve a specific biological microscopic process. The prepared C-dots were discovered to be able to be used in DNA extraction without affecting DNA cleavage; in addition, they can be used in semi-3D cell culture especially for cancer cells. These electrically charged C-dots@glass beads developed in the present work showed a great potential in diagnosis and drug delivery targeting tumor cells.