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In JoVE (1)
Other Publications (7)
Articles by Kai Ruan in JoVE
JoVE Neuroscience
Assaying Locomotor, Learning, and Memory Deficits in Drosophila Models of Neurodegeneration
Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine
Behavior assays for measuring locomotor functions, learning, and memory abilities in Drosophila.
Other articles by Kai Ruan on PubMed
The Multifaceted Role of Periostin in Tumorigenesis
Periostin, also called osteoblast-specific factor 2 (OSF-2), is a member of the fasciclin family and a disulfide-linked cell adhesion protein that has been shown to be expressed preferentially in the periosteum and periodontal ligaments, where it acts as a critical regulator of bone and tooth formation and maintenance. Furthermore, periostin plays an important role in cardiac development. Recent clinical evidence has also revealed that periostin is involved in the development of various tumors, such as breast, lung, colon, pancreatic, and ovarian cancers. Periostin interacts with multiple cell-surface receptors, most notably integrins, and signals mainly via the PI3-K/Akt and other pathways to promote cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, aspects related to the function of periostin in tumorigenesis are summarized.
Upregulated Expression of Periostin by Hypoxia in Non-small-cell Lung Cancer Cells Promotes Cell Survival Via the Akt/PKB Pathway
Periostin is a secreted protein and has been shown to be frequently overexpressed in various types of human cancers. We have previously reported that periostin potently promotes metastatic growth of colon cancer by augmenting cell survival. However, little is known about the functions of periostin in non-small-cell lung cancer. Here, we revealed that increased expression of periostin in non-small-cell lung cancer A549 cells was one kind of cellular responses to the stress of chemical-mimic hypoxia, and this effect could be regulated by hypoxia inducible growth factors, such as TGF-alpha and bFGF. We further demonstrated that RTK/PI3-K pathway activated by TGF-alpha and bFGF was evoked in upregulating the expression of periostin, and then periostin promoted the survival of A549 cells under hypoxic microenvironment via activation of Akt/PKB pathway. Therefore, periostin and the pathway that it involved might provide a target for lung cancer treatment.
MicroRNAs: Novel Regulators in the Hallmarks of Human Cancer
MicroRNAs (miRNAs) are small non-coding RNAs of 18-25 nucleotides in length that function as negative regulators. miRNAs post-transcriptionally regulate gene expression by either inhibiting mRNA translation or inducing mRNA degradation, and participate in a wide variety of physiological and pathological cellular processes. Recent reports have revealed that the deregulation of miRNAs correlates with various human cancers and is involved in the initiation and progression of human cancers. miRNAs can act as oncogenes or tumor suppressors to inhibit the expression of cancer-related target genes and to promote or suppress tumorigenesis in various tissues. Therefore, abnormal miRNA expression can be regarded as a common feature of human cancers, and the identification of miRNAs and their respective targets may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic strategies to treat cancers. In the present review, we discuss the emerging roles of miRNAs in the hallmarks of human cancers.
Role of Hypoxia in the Hallmarks of Human Cancer
Hypoxia has been recognized as one of the fundamentally important features of solid tumors and plays a critical role in various cellular and physiologic events, including cell proliferation, survival, angiogenesis, immunosurveillance, metabolism, as well as tumor invasion and metastasis. These responses to hypoxia are at least partially orchestrated by activation of the hypoxia-inducible factors (HIFs). HIF-1 is a key regulator of the response of mammalian cells to oxygen deprivation and plays critical roles in the adaptation of tumor cells to a hypoxic microenvironment. Hypoxia and overexpression of HIF-1 have been associated with radiation therapy and chemotherapy resistance, an increased risk of invasion and metastasis, and a poor clinical prognosis of solid tumors. The discovery of HIF-1 signaling has led to a rapidly increasing understanding of the complex mechanisms involved in tumor hypoxia and has helped greatly in screening novel anticancer agents. In this review, we will first introduce the cellular responses to hypoxia and HIF-1 signaling pathway in hypoxia, and then summarize the multifaceted role of hypoxia in the hallmarks of human cancers.
Genistein Induces G2/M Cell Cycle Arrest and Apoptosis of Human Ovarian Cancer Cells Via Activation of DNA Damage Checkpoint Pathways
Genistein is a major isoflavonoid in dietary soybean, commonly consumed in Asia. Genistein exerts inhibitory effects on the proliferation of various cancer cells and plays an important role in cancer prevention. However, the molecular and cellular mechanisms of genistein on human ovarian cancer cells are still little known. We show that exposure of human ovarian cancer HO-8910 cells to genistein induces DNA damage, and triggers G2/M phase arrest and apoptosis. Furthermore, we also found that checkpoint proteins ATM and ATR are phosphorylated and activated in the cells treated with genistein. It is also shown that genistein increases the phosphorylation and activation of Chk1 and Chk2, which results in the phosphorylation and inactivation of phosphatases Cdc25C and Cdc25A, and thereby the phosphorylation and inactivation of Cdc2 which arrests cells in G2/M phase. Moreover, genistein enhances the phosphorylation and activation of p53, while decreases the ratio of Bcl-2/Bax and Bcl-xL/Bax and the level of phosphorylated Akt, which result in cells undergoing apoptosis. These results demonstrate that genistein-activated ATM-Chk2-Cdc25 and ATR-Chk1-Cdc25 DNA damage checkpoint pathways can arrest ovarian cancer cells in G2/M phase, and induce apoptosis while the cellular DNA damage is too serious to be repaired. Thus, the antiproliferative, DNA damage-inducing and pro-apoptotic activities of genistein are probably responsible for its genotoxic effects on human ovarian cancer HO-8910 cells.
Cavitation Effect of Holmium Laser Pulse Applied to Ablation of Hard Tissue Underwater
To overcome the inconsecutive drawback of shadow and schlieren photography, the complete dynamics of cavitation bubble oscillation or ablation products induced by a single holmium laser pulse [2.12 microm, 300 micros (FWHM)] transmitted in different core diameter (200, 400, and 600 microm) fibers is recorded by means of high-speed photography. Consecutive images from high-speed cameras can stand for the true and complete process of laser-water or laser-tissue interaction. Both laser pulse energy and fiber diameter determine cavitation bubble size, which further determines acoustic transient amplitudes. Based on the pictures taken by high-speed camera and scanned by an optical coherent microscopy (OCM) system, it is easily seen that the liquid layer at the distal end of the fiber plays an important role during the process of laser-tissue interaction, which can increase ablation efficiency, decrease heat side effects, and reduce cost.
NMNAT Suppresses Tau-induced Neurodegeneration by Promoting Clearance of Hyperphosphorylated Tau Oligomers in a Drosophila Model of Tauopathy
Tauopathies, including Alzheimer's disease, are a group of neurodegenerative diseases characterized by abnormal tau hyperphosphorylation that leads to formation of neurofibrillary tangles. Drosophila models of tauopathy display prominent features of the human disease including compromised lifespan, impairments of learning, memory and locomotor functions and age-dependent neurodegeneration visible as vacuolization. Here, we use a Drosophila model of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), in order to study the neuroprotective capacity of a recently identified neuronal maintenance factor, nicotinamide mononucleotide (NAD) adenylyl transferase (NMNAT), a protein that has both NAD synthase and chaperone function. NMNAT is essential for maintaining neuronal integrity under normal conditions and has been shown to protect against several neurodegenerative conditions. However, its protective role in tauopathy has not been examined. Here, we show that overexpression of NMNAT significantly suppresses both behavioral and morphological deficits associated with tauopathy by means of reducing the levels of hyperphosphorylated tau oligomers. Importantly, the protective activity of NMNAT protein is independent of its NAD synthesis activity, indicating a role for direct protein-protein interaction. Next, we show that NMNAT interacts with phosphorylated tau in vivo and promotes the ubiquitination and clearance of toxic tau species. Consequently, apoptosis activation was significantly reduced in brains overexpressing NMNAT, and neurodegeneration was suppressed. Our report on the molecular basis of NMNAT-mediated neuroprotection in tauopathies opens future investigation of this factor in other protein foldopathies.
