A Review of Centriole Activity, and Wrongful Activity, during Cell Division

This is a review paper on centriole behavior and their role in enabling cell division and duplication. The paper is based primarily on articles published in this, the 21st century. Following a description of centriole geometry, the paper discusses centriole duplication and the ensuring events leading to cell division. From a structural perspective each centriole is seen to be a cylindrical composition of nine blades, each having three microtubules which are themselves hollow cylinders approximately 400 nm long, with inner and outer diameters of 15 and 25 nm. The paper then discusses the nucleation of these microtubules. The paper concludes with a description of centriole malfunction and overduplication (supernumerary centrioles), leading to clusters of centrioles —a hallmark of cancer cells. These centriole clusters thus form “biomarkers” for tumor imaging and treatment.

Mechanics of Centriole Microtubules

This is a review paper describing recent findings about the physical properties of centriolar microtubules. Microtubules are the principal structures making up the centrioles. The centrioles in turn are the principal agents in cell duplication and division (mitosis). The microtubules are seen to be long hollow cylinders: approximately 400 nm in length, with a 24 nm outside diameter, and a 5 nm wall thickness. Within the centrioles, the microtubules are arranged into nine parallel sets of triplets—thus numbering 27 parallel cylinders per centriole. Each normal eukaryotic (human and animal) cell, not in mitosis, has two perpendicular centrioles connected at their proximal (base) ends. During mitosis, these two become four, resulting in a total of 108 centriolar microtubules. The structure of the microtubules themselves is found to consist of 13 parallel filaments making up the cylinder walls. The filaments are composed of approximately 40 and β-tubulin connected end-to-end with their proximal (base) ends anchored in γ-tubulin. The longitudinal vibrations of the filaments are believed to create an electro-magnetic field within the cell which plays an important role in mitosis.

A Review of Electromagnetic Activity in Cellular Mechanics

This is a review of recent literature concerning electromagnetic effects on cellular mechanics. “Recent” refers primarily to papers published in this (the 21st) century. The review shows that there are relatively few papers on cellular electromagnetics as compared with those on proteins, biochemistry, and cellular anatomy. The principal finding of the reviewed papers is that cellular electromagnetic fields appear to arise from longitudinal vibrations of the filaments making up the walls of the microtubules. Microtubules are long hollow cylinders which form the overall structure of the centrioles. The microtubules, and therefore the centrioles themselves, are arranged in nine sets of parallel blades with each blade having three microtubules. The centrioles occur in pairs perpendicularly to each other. During mitosis (cell division) the centriole pair becomes two pair which then separate and divide the cell into two. It seems that electromagnetic forces play a central role in this division. Electromagnetic activity in wound healing and in the imaging and treatment of tumors is discussed.

Using the Electromagnetics of Cancer’s Centrosome Clusters to Attract Therapeutic Nanoparticles

This paper summarizes recent research findings concerning centrioles, centriole duplication, centriole overduplication, supernumerary centrioles, centrosomes, and centrosome amplification. The paper then discusses the status of ongoing research on the use of nanoparticles for cancer treatment. The research findings show that a centriole produces an electromagnetic field apparently due to the longitudinal oscillation of its microtubules (MTs). A cluster of centrioles is therefore presumed to produce an enhanced electromagnetic field. Individual centrioles are immersed in a cloud of electron-dense material (proteins) which together with the centrioles is known as the centrosome. A cluster of centrioles thus produces a cluster of centrosomes—a hallmark of cancer cells. With enhanced electromagnetic fields, centrosome clusters provide an attraction for magnetically charged nanoparticles. These nanoparticles however are not attracted to normal cells which with only two (or at most four) centrioles, have a weaker magnetic field. The idea is simple: Magnetized and therapeutic nanoparticles are directed toward tumors and then attracted to the centrosome clusters of the tumor cells. Once inside the tumor cells, the nanoparticles can release their toxins.

Chromosomes and Centrosomes—Team Players in Cell Division

This paper provides a mid-level description of cell division and duplication. The focus is on the roles by the chromosomes, centrosomes, microtubules and the kinetochores. The emphasis is on the mechanical activity and the resulting physical developments. The paper also provides, in its discussion, the harmful effects occurring when duplication procedures go awry. This often leads to unwanted duplication and possibly cancer.

KDELR2 promotes breast cancer proliferation via HDAC3-mediated cell cycle progression

Background:Histone deacetylases(HDACs)engage in the regulation of various cellular processes by controlling global gene expression.The dysregulation of HDACs leads to carcinogenesis,making HDACs ideal targets for cancer therapy.However,the use of HDAC inhibitors(HDACi)as single agents has been shown to have limited success in treating solid tumors in clinical studies.This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy.Methods:Transcriptome sequencing and bioinformatics analysis were performed to screen for genes responsive toHDACi in breast cancer cells.The effects of HDACi on cell viability were detected using the MTT assay.The mRNA and protein levels of genes were determined by quantitative reverse transcription-PCR(qRT-PCR)andWestern blotting.Cell cycle distribution and apoptosis were analyzed by flow cytometry.The binding of CREB1(cAMP-response element binding protein 1)to the promoter of the KDELR(The KDEL(Lys-Asp-Glu-Leu)receptor)gene was validated by the ChIP(chromatin immunoprecipitation assay).The association between KDELR2 and protein of centriole 5(POC5)was detected by immunoprecipitation.A breast cancer-bearing mouse model was employed to analyze the effect of the HDAC3-KDELR2 axis on tumor growth.Results:KDELR2 was identified as a novel target of HDAC3,and its aberrant expression indicated the poor prognosis of breast cancer patients.We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients.The results of the ChIP assay and qRT-PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1.The HDAC3-KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation.Moreover,the HDAC3-KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo.Conclusion:Our results uncovered a previously unappreciated function of KDELR2 in tumorigenesis,linking a critical Golgi-the endoplasmic reticulum traffic transport protein to HDAC-controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer.