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Atherosclerosis (AS) is a common chronic inflammatory disease of the arteries, which is closely related to dyslipidemia, inflammatory factors, and oxidative stress. Poria cocos polysaccharides (PCP) are one of the main active ingredients of Poria, which has significant pharmacological effects. In this study, the potential protective mechanism of PCP on AS was discussed in the ApoE-/- mice model induced by high-fat diet. These pathological changes were evaluated by H&E and oil red O staining. The levels of pro-inflammatory cytokines in aortic tissue were measured by enzyme-linked immunosorbent assay kit. These protein expressions were detected by Western blot and immunohistochemistry. The results showed that PCP inhibited the serum inflammatory mediators (tumor necrosis factor-α, interleukin-6, and nitric oxide) and lipids (low-density lipoprotein-cholesterol, triglyceride, and total cholesterol) increase. Moreover, PCP also reduced the concentration of malondialdehyde, increased the activity of superoxide dismutase, and improved the pathological changes of the aorta. Finally, PCP inhibited the activation of the TLR4/NF-κB pathway in the aorta and blocked the expression of matrix metalloproteinase 2 and intercellular adhesion molecule 1 proteins. In short, PCP intervenes in AS by reducing inflammatory factors and blood lipid levels.

The retention of triterpenoids in the C18 column and apparent formation constants of triterpenoids with cyclodextrins (CDs) were studied using HPLC. As the effective mobile phase additives, CDs can improve the separation of triterpenoid glycosides (asiaticoside B, madecassoside and asiaticoside) and reduce the retention of triterpenoids, and it is attributed to that triterpenoids forms a 1:1 inclusion complexes with CDs. The apparent formation constants of these complexes depend on the structure of triterpenoids, as well as on the substituent group and the hydrophobic cavity size of CDs. Triterpenoid glycosides had less apparent formation constants with HP-β-CD and Glu-β-CD, which might be related that hydroxypropyl group and glucose group in the structure of HP-β-CD and Glu-β-CD were unfaver to formation of the inclusion complexes. Asiaticoside B had larger apparent formation constants with CDs than madecassoside and asiaticoside. Larger apparent association constants of triterpenoid acids (madecassic acid and asiatic acid) were obtained with γ-CD than β-CD and its derivatives, which are related that triterpenoid acids fit well into the γ-CD cavity, and form relatively stable inclusion complexes. The ∆G (25 °C), ∆H and ∆S reveal that the inclusion processes between triterpenoids and CDs were not spontaneous, exothermic, and enthalpically driven. In addition, the usefulness of CDs for simultaneous analysis of five triterpenoids in HPLC and drug delivery vehicles was described.

Background: The cGAS (GMP-AMP synthase)-triggered senescence-associated secretory phenotype (SASP) in promotion of cancer progression has been extensively documented. However, the role of cGAS-mediated DNA autophagy is little evaluated in cancer cells.Methods: Immunofluorescence, senescence associated-β-galactosidase staining (SA-β-gal) and Western blot were performed to detect gene expression, distribution and phenotypes. PCR, IP-PCR, FISH, BrdU, Comet assay, coimmunoprecipitation, sucrose density gradient centrifugation were carried out to detect possible mechanisms. Trypan blue exclusion, Live/dead staining and MTS assay were to measure the cell viability. All analyses were performed using GraphPad Prism 8. Relationships were analyzed using t-tests. A P-value of less than 0.05 was considered significant. All statistical tests and P values were 2-sided, and the level of significance was set at Results: Active DNA autophagy but not SASP activity could be detected in the BT-549 breast cancer cells with high micronucleus (MN). The selective autophagy of free genomic DNA in the cytoplasm is mediated by cGAS and usually coordinated with SQSTM1-mediated autophagy of ubiquitinated histones. Cytoplasmic DNA together with nuclear proteins derive from DNA replication-induced nuclear damage and MN collapse. The inhibition of DNA autophagy through either chemical inhibitors or genomic silencing of cGAS or SQSTM1 suppresses the growth and survival of cancer cells, while enhanced DNA damage increases the sensitivity to these inhibitors. Human cancer cells with either high DNA autophagy or enhancement of DNA damage are sensitive to inhibition of DNA autophagy.Conclusions: Our investigation revealed DNA autophagy in breast cancer cells with high MN formation. Autophagy of genomic DNA in the cytosol could be mediated by cGAS but is usually coordinated with other autophagic mediators. The selective autophagy mediated clearance of free genomic DNA protects of growth and survival cancer cells, and autophagic inhibition could be a potential therapeutic approach for cancer cells with high DNA autophagic activity.

Triterpenes are considered the major active components in Centella asiatica (L.) Urb. (C. asiatica), such as asiatic acid, madecassic acid, asiaticoside, madecassoside and asiaticoside B. It is difficult to simultaneously determine five triterpenes because of madecassoside isomers (madecassoside and asiaticoside B), and the great polarity difference between triterpene acid and triterpene glycoside. In this study, a simple high performance liquid chromatography method with isocratic elution employing cyclodextrins (CDs) as the mobile phase additives was developed to determine five triterpenes in C. asiatica. Various factors affecting triterpenes retention in the C18 column, such as the nature of CDs, γ-CD concentration, acetonitrile percentage and temperature, were studied. Experimental results showed that γ-CD, as an effective mobile phase additive, could markedly reduce the retention of triterpenes (especially asiatic acid and madecassic acid), and improve the separation for madecassoside and asiaticoside B. The elution of five triterpenes could be achieved on an ODS C18 column within 30 min using the acetonitrile-0.2% phosphoric acid contained 4.0 mM γ-CD (20:80, v/v) mixture as the mobile phase. The retention modification of triterpenes may be attributed to the formation of the triterpenes-γ-CD inclusion complexes. The optimized method was successfully applied for simultaneous determination of five triterpenes in C. asiatica.

Summary Root‐associated microbiomes play significant roles in plant productivity, health and ecological services. However, our current understanding of the microbial assemblages in the rhizosphere and endosphere of herbage is still limited. To gain insights into these microbial assemblages, Illumina MiSeq high‐throughput sequencing was performed to investigate the characteristics of microbial communities of an herbage, Leymus chinensis. Hierarchical clustering analysis and principal coordinate analysis (PCoA) results showed that microbial communities of the rhizosphere and endosphere samples were clearly distinguished. Rhizosphere soil communities showed a greater sensitivity than root endosphere communities using linear discriminant analysis (LDA) effect size (LEfSe). Rhizosphere and endosphere communities performed their respective functions in the soil as a cohesive collective, and Rhizobiales were observed to function as generalists. Redundancy analysis (RDA) and variance partitioning analysis (VPA) results revealed that the contribution of the interaction between soil physicochemical parameters and soil enzymes was greater than their individual contributions. In summary, this study is the first to elucidate the microbial diversity and community structure of L. chinensis and compare the diversity and composition between rhizospheric and endosphere microbiomes., In the root‐associated microbiomes of Leymus chinensis, the sensitivity of the fungal community was higher than that of the bacterial community, and rhizosphere soil communities showed a greater sensitivity than root endosphere communities. Rhizobiales members were observed to function as generalists in the root‐associated interaction network, and the rhizosphere and endosphere communities performed their respective functions in the soil as a cohesive collective. Moreover, root soil ‐associated microbiomes of L. chinensis were significantly affected by the interaction of soil physicochemical parameters and soil enzymes.

Camelina protein is a major by-product created after oil extraction from camelina seeds; it has drawn research attention as an economical material for bio-industrial implications. The present study investigates the influence of polyelectrolyte interaction on camelina protein structure and effects on wood bonding performance when used as a bio-adhesive. Infrared spectroscopy (IR) and transmission electron microscopy (TEM) images revealed that after interacting with polymeric amine epichlorohydrin (PAE), a cationic polyelectrolyte, camelina protein is partly unfolded with more flexible chain structures. PAE works as a bridge among different protein molecules primarily through electrostatic and hydrophobic interactions. Separation by size exclusion chromatography showed that soluble PAE modified proteins are smaller in molecular size. Polymeric amine epichlorohydrin modified proteins had reduced solubility, possibly indicating increased hydrophobicity. The PAE treatment of camelina protein greatly improved both dry and wet adhesion strength when used as an adhesive. Dry bond strength increased from 2.39 ± 0.52 MPa to 5.39 ± 0.50 MPa with 100% wood failure and wet bond strength was dramatically increased from 0.37 ± 0.22 to 2.35 ± 0.17 MPa on two layer cherry wood tests. Two aliphatic structures with hydrophobic chains were introduced into the PAE modified protein system to further improve water resistance and get wet bond strength increase from 0 to 1.30 ± 0.23 MPa on three layer yellow pine wood tests. This study demonstrates the possibility of camelina as a green resource for the adhesive industry.

Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis. In addition, phosphorylated LRP6 was positively correlated with nuclear accumulation of β-catenin. Overexpression or activation of LRP6 could activate Wnt signaling and promote tumor cell migration in vitro. The activation of LRP6 could induce microtubule dynamics and actin remodeling, probably through regulation of microtubule-associated protein 1B (MAP1B), microtubule actin cross-linking factor 1 (MACF1) and Rho GTPase--RhoA and Rac1. The investigation suggests that LRP6 may be a potential prognostic marker and therapeutic target in the progression of colorectal cancers.

Background Human epidermal growth factor receptor (EGFR) is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR mutations. Although there are many reports for some individual cancers, comprehensive profiling of EGFR mutations, overexpression, amplification, DNA methylation, and their clinical associations across many different cancers simultaneously was not available. This study aimed to fill the gap and provide insights to the alteration spectrum of EGFR and its therapeutic and prognostic implications. Methods The Cancer Genome Atlas (TCGA) datasets for 32 cancer types involving 11,314 patients were analyzed for alterations (mutations and amplification/deletion), abnormal expression and DNA methylation in EGFR gene. Mutation frequency, genomic location distribution, functional impact, and clinical targeted therapy implication were compared among different cancer types, and their associations with patient survival were analyzed. Results EGFR alteration frequency, mutation sites across functional domains, amplification, overexpression, and DNA methylation patterns differed greatly among different cancer types. The overall mutation frequency in all cancers combined was relatively low. Targetable mutations, mainly in lung cancer, were primarily found in the Pkinase_Tyr domain. Glioblastoma multiforme had the highest rate of alterations, but it was dominated by gene amplification and most mutations were in the Furin‐like domain where targeted therapy was less effective. Low‐grade glioma often had gene amplification and increased EGFR expression which was associated with poor outcome. Colon and pancreatic adenocarcinoma had very few EGFR mutations; however, high EGFR expression was significantly associated with short patient survival. Squamous cell carcinoma regardless of their sites (the head and neck, lung, or esophagus) exhibited similar characteristics with an alteration frequency of about 5.0%, was dominated by gene amplification, and had increased EGFR expression generally associated with short patient survival. DNA methylation was highly associated with EGFR expression and patient outcomes in some cancers. Conclusions EGFR aberration type, frequency, distribution in functional domains, and expression vary from cancer to cancer. While mutations in the Pkinase_Tyr domain are more important for treatment selection, increased expression from amplification or deregulation affects more tumor types and leads to worse outcome, which calls for new treatment strategies for these EGFR‐driven tumors.

ObjectiveFamilial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of adenomas at different evolutionary stages in the colon and rectum that will inevitably progress to adenocarcinomas if left untreated. Here, we investigated the genetic alterations and transcriptomic transitions from precancerous adenoma to carcinoma.DesignWhole-exome sequencing, whole-genome sequencing and single-cell RNA sequencing were performed on matched adjacent normal tissues, multiregionally sampled adenomas at different stages and carcinomas from six patients with FAP and one patient with MUTYH-associated polyposis (n=56 exomes, n=56 genomes and n=8,757 single cells). Genomic alterations (including copy number alterations and somatic mutations), clonal architectures and transcriptome dynamics during adenocarcinoma carcinogenesis were comprehensively investigated.ResultsGenomic evolutionary analysis showed that adjacent lesions from the same patient with FAP can originate from the same cancer-primed cell. In addition, the tricarboxylic acid cycle pathway was strongly repressed in adenomas and was then slightly alleviated in carcinomas. Cells from the ‘normal’ colon epithelium of patients with FAP already showed metabolic reprogramming compared with cells from the normal colon epithelium of patients with sporadic colorectal cancer.ConclusionsThe process described in the previously reported field cancerisation model also occurs in patients with FAP and can contribute to the formation of adjacent lesions in patients with FAP. Reprogramming of carbohydrate metabolism has already occurred at the precancerous adenoma stage. Our study provides an accurate picture of the genomic and transcriptomic landscapes during the initiation and progression of carcinogenesis, especially during the transition from adenoma to carcinoma.

Volcanic cones, as essential components of the terrestrial ecosystem, provide an excellent model for studying the soil formation process, fertility and structure. However, there have not been any studies comparing soil microbial differences between cinder cones and spatter cones. To complement this lack of knowledge, we characterized the compositions of soil microbiomes between cinder cone and spatter cone sites using Illumina MiSeq high-throughput sequencing. Compared with spatter cone sites, cinder cone sites had higher microbial richness and greater abundance of arbuscular mycorrhizal (AM) fungi, which were found to work as keystone taxa. The cooccurrence network showed more complex interspecies relationships in spatter cone than in cinder cone; however, there was a larger proportion of positive correlations in cinder cone than in spatter cone. The functional composition profiles indicated that carbohydrate metabolism and amino acid metabolism were significantly enhanced in spatter cone and that there was a strong positive correlation between the two. Soil fungal communities were likely to be more resilient and resistant to Wulanhada volcanic activity than bacterial communities, which may have been due to the effects of the larger number of keystone taxa in soil fungal communities. Structural equation modeling (SEM) demonstrated that aboveground biomass and soil moisture exerted a significant impact on soil microbial communities and that alpha diversity was the biggest positive contributor of microbial multifunctionality. Our findings indicate the prospect of exploring the characteristics of the soil microbial communities in volcanoes of different types.

Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase and regulates a variety of biological processes. Recent studies show GSK-3β can regulate pre-mRNA processing and transcription through phosphorylation of multiple splicing factors, but the detailed mechanism is still undetermined. In this study, we further proved that GSK-3β could specifically co-localize with SC35 in nuclear speckles depending on its kinase activity. Immunofluorescence and FISH studies showed the activity of nuclear GSK-3β regulated the assembly of nuclear speckles and consequently modulated the post-transcriptional processing of mRNA. In addition, GSK-3β phosphorylated SC35 and promoted its hyperphosphorylation, in which the unique C-terminal sequences were particularly important to efficiently sequential multiple phosphorylation of SC35. Hyperphosphorylated SC35 converged into cluster and lost its ability to perform splicing in nuclear speckles. More importantly, the nuclear GSK-3β activity could be a part of Wnt/β-catenin signaling activation by TCF4 and might take part in embryonic or tumorigenesis of cells.

Purpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution. Experimental Design: The expression and subcellular redistribution of NAT10, β-catenin, E-cadherin, and GSK-3β were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3β, transfection of wild-type or kinase-inactivated GSK-3β, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays. Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive “leading edge” of the tumor. This correlated well with nuclear accumulation of β-catenin (P < 0.001; χ2 = 68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values < 0.001), and was associated with a poorer prognosis (P = 0.023; χ2 = 5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3β. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility. Conclusion: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3β activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma. Clin Cancer Res; 20(17); 4717–29. ©2014 AACR.

Flowering is one of the most important steps in the life cycle of a plant. Plants utilize light as a source of information to determine the timing of flowering. Recent molecular genetics studies have implicated phytochrome B (PhyB)-mediated responses to light in the control of floral transition. However, the molecular mechanism by which ZmPhyB2 mediates flowering time remains uncertain, although it is known to control the photoperiod-dependent floral transition in maize. In this study, an “rpt_family” (MITE) sequence was detected in the ZmPhyB2 promoter region of early flowering maize. The presence or absence of the MITE was associated with phenotypic variation of the flowering time following association analysis. ZmPhyB2 transcript levels were expressed rhythmically under short-day (SD) conditions, with two relatively sharp peaks. The mRNA expression of ZmPHYB2 was higher in CML288 (without MITE) than in B73 (with MITE). The two peaks appeared ~3 h earlier in ZmPhyB2 expression from CML288 and slightly ahead of time from B73, and ZmPhyB2 expression increased dramatically in CML288 and increased slightly in B73 following 30-min night break (NB) treatments under SD conditions. The results showed that the ZmPhyB2 allele without MITE insertion was associated with dramatically enhanced gene expression following an NB treatment under SD conditions, resulting in a delayed flowering time, which suggested that the MITE insertion functioned as a repressor of gene expression. In addition, our findings showed that ZmPhyB2 peaked earlier after the NB treatment, with an increase in the accumulation of ZmCCA1 mRNA, giving rise to a longer circadian clock period. The longer circadian clock period produced two peak expression patterns of Zmconz1, which further inhibited ZmZCN8 expression, which may result in flowering delay.

Investigation of a serious pig disease with high mortality and typical lung lesions yielded a bacterial isolate identified as Providencia alcalifaciens based on the 16S ribosomal DNA sequence analysis. The pathogenicity of this bacterial isolate was confirmed in piglets and mice. The bacterial strain caused the typical illness in piglets, which suffered serious dyspnea and hemorrhagic pneumonia. The drug resistance spectrum of the bacterium was also determined. The results indicated that the isolate is resistant to 12 antibiotics and intermediately resistant to 10 antibiotics out of the 34 antibiotics tested. The current study is the first to report a serious lung disease in piglets caused by a multidrug resistant P. alcalifaciens isolate, which should be given more attention during surveillance and diagnostics.

SSX, a family of genes clustered on the X chromosome, has been identified as a cancer-testis antigen and also forms a part of the SYT-SSX fusion gene found in synovial sarcoma, implying that it has an important role in tumorigenesis. However, knowledge of the molecular regulation of SSX is still limited. In this study, we demonstrate that SSX or its SYT fusion protein is distributed as nuclear speckles, in which it is co-localized with B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1), which is a core factor of polycomb repressor complex 1. The C-terminal residues of SSX are indispensable for the nuclear speckle distribution, while the N-terminal domain is necessary for the recruitment of Bmi1, indicating that intact SSX must be needed for interaction with Bmi1 both spatially and functionally. In addition, the N-terminus of SSX also proved to contain an intrinsic nucleolar localization signal, which mediates the nucleolar translocation of SSX in particular kinds of cell stress such as the oxidation of hydrogen peroxide or heat shock. This stress-induced translocation is reversible and accompanied by HSP 70 or p14ARF traffic, suggesting that SSX is a stress response gene. It is of note that nucleolar translocation of SSX can result in disassociation of SSX from Bmi1, with consequent down-regulation of Bmi1 activity. These novel findings regarding distinct domains of SSX and its interaction with Bmi1 may shed light on the mechanism by which synovial sarcoma develops and on the up-regulation of SSX in cancer cells.

Ewing sarcoma (ES) is the second most common malignant bone and soft tissue tumor in children and adolescents. Despite advances in comprehensive treatment, patients with ES metastases still suffer poor outcomes, thus, emphasizing the need for detailed genetic profiles of ES patients to identify suitable molecular biomarkers for improved prognosis and development of effective and targeted therapies. In this study, the next generation sequencing Ion AmpliSeq™ Cancer Hotspot Panel v2 was used to identify cancer-related gene mutations in the tissue samples from 20 ES patients. This platform targeted 207 amplicons of 2800 loci in 50 cancer-related genes. Among the 20 tissue specimens, 62 nonsynonymous hotspot mutations were identified in 26 cancer-related genes, revealing the molecular heterogeneity of ES. Among these, five novel mutations in cancer-related genes (KDR, STK11, MLH1, KRAS, and PTPN11) were detected in ES, and these mutations were confirmed with traditional Sanger sequencing. ES patients with KDR, STK11, and MLH1 mutations had higher Ki-67 proliferation indices than the ES patients lacking such mutations. Notably, more than half of the ES patients harbored one or two possible 'druggable' mutations that have been previously linked to a clinical cancer treatment option. Our results provided the foundation to not only elucidate possible mechanisms involved in ES pathogenesis but also indicated the utility of Ion Torrent sequencing as a sensitive and cost-effective tool to screen key oncogenes and tumor suppressors in order to develop personalized therapy for ES patients.

NAT10 (N-acetyltransferase 10) is a protein with histone acetylation activity and primarily identified to be involved in regulation of telomerase activity. The presented research shows its transcriptional activation by genotoxic agents and possible role in DNA damage. NAT10 mRNA could be markedly increased by using hydrogen peroxide (H2O2) or cisplatin in a dose- and time-dependent way, and the immunofluorescent staining revealed that the treatment of H2O2 or cisplatin induced focal accumulation of NAT10 protein in cellular nuclei. Both H2O2 and cisplatin could stimulate the transcriptional activity of the NAT10 promoter through the upstream sequences from -615 bp to +110 bp, with which some nuclear proteins interacted. Ectopic expression of NAT10 could enhance the number of survival cells in the presence of H2O2 or cisplatin. The above results suggested that NAT10 could be involved in DNA damage response and increased cellular resistance to genotoxicity.

To isolate proteins involved in hTERT transcriptional regulation, the HeLa cDNA library was screened using the hTERT promoter-based yeast one-hybrid assay. A positive clone was rescued and proved to contain an open reading frame and the upstream coding sequences were obtained by 5'-RACE. The assembled full cDNA consisted of a 2.5 kb reading frame encoding 834 amino acids, in which a conserved N-acetyltransferase domain (GNAT family) was searched out in bioinformatics, and thus named as hALP (human N-acetyltransferase-like protein, GenBank Accession No. AF 489535). The expression of native hALP was identified in HeLa cells and proved to distribute in the cellular nucleus. The binding potential of hALP to hTERT promoter was confirmed by EMSA and the interacting sequence involved to -201- to -56-nt upstream region of the promoter. On transfection assay, hALP could obviously transactivate hTERT promoter and stimulate endogenous telomerase activity of cells. The analysis on histone acetyltransferase showed that hALP could specifically acetylate free histones in vitro. The investigation suggested that hALP influences the activity of histone acetylation and could up-regulate telomerase activity through transactivation of hTERT promoter.

Centrosome amplification, which is a characteristic of cancer cells, has been understood as a driving force of genetic instability in the development of cancer. In previous work, we demonstrated that TEIF (transcriptional element-interacting factor) distributes in the centrosomes and regulates centrosome status under both physiologic and pathologic conditions. Here we identify TEIF as a downstream effector in EGF/PI3K/Akt signaling. The addition of EGF or transfection of active Akt stimulates centrosome TEIF distribution, resulting in an increase of centrosome splitting and amplification, while inhibitors of either PI3K or Akt attenuate these changes in TEIF and the associated centrosome status. A consensus motif for Akt phosphorylation (RHRVLT) proved to be involved in centrosomal TEIF localization, and the 469-threonine of this motif may be phosphorylated by Akt both in vitro and in vivo. Elimination of this phosphorylated site on TEIF caused reduced centrosome distribution and centrosome splitting or amplification. Moreover, TEIF closely co-localized with C-NAP1 at the proximal ends of centrioles, and centriolar loading of TEIF stimulated by EGF/Akt could displace C-NAP1, resulting in centrosome splitting. These findings reveal linkage of the EGF/PI3K/Akt signaling pathway to regulation of centrosome status which may act as an oncogenic pathway and induce genetic instability in carcinogenesis.