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Protein kinase C zeta and cancer

Ravi K Deevi, Jane McClements, Karen D McCloskey, Aliya Fatehullah, Dorota Tkocz, Arman Javadi, Robyn Higginson, Victoria Marsh Durban, Marnix Jansen, Alan Clarke, Maurice B Loughrey, Frederick C Campbell
Development of cribriform morphology (CM) heralds malignant change in human colon but lack of mechanistic understanding hampers preventive therapy. This study investigated CM pathobiology in three-dimensional (3D) Caco-2 culture models of colorectal glandular architecture, assessed translational relevance and tested effects of 1,25(OH)2D3,theactive form of vitamin D. CM evolution was driven by oncogenic perturbation of the apical polarity (AP) complex comprising PTEN, CDC42 and PRKCZ (phosphatase and tensin homolog, cell division cycle 42 and protein kinase C zeta)...
April 20, 2016: Oncotarget
Ana Santos Cravo, Edward Carter, Mert Erkan, Emma Harvey, Makoto Furutani-Seiki, Randall Mrsny
External adherens junction-based cell-cell contacts involving E-cadherin interactions function to sense planar cell status and modulate epithelial cell proliferation through Hippo (Hpo) and non-canonical Wnt pathways signaling. We hypothesized these regulatory processes should also be sensitive to a similar cell-cell contact sensor associated with apical-basal polarity events at epithelial surfaces. We used 2 human pancreatic cancer cell lines to explore this hypothesis: one with the capacity to form functional tight junction structures and polarize (HPAFII) and one lacking this capacity (AsPc1)...
July 2015: Tissue Barriers
Arindam Paul, Marsha Danley, Biswarup Saha, Ossama Tawfik, Soumen Paul
Atypical Protein Kinase C zeta (PKCζ) forms Partitioning-defective (PAR) polarity complex for apico-basal distribution of membrane proteins essential to maintain normal cellular junctional complexes and tissue homeostasis. Consistently, tumor suppressive role of PKCζ has been established for multiple human cancers. However, recent studies also indicate pro-oncogenic function of PKCζ without firm understanding of detailed molecular mechanism. Here we report a possible mechanism of oncogenic PKCζ signaling in the context of breast cancer...
2015: Scientific Reports
Amanda M Butler, Michele L Scotti Buzhardt, Eda Erdogan, Shuhua Li, Kristin S Inman, Alan P Fields, Nicole R Murray
Pancreatic cancer is highly resistant to current chemotherapies. Identification of the critical signaling pathways that mediate pancreatic cancer transformed growth is necessary for the development of more effective therapeutic treatments. Recently, we demonstrated that protein kinase C iota (PKCι) and zeta (PKCζ) promote pancreatic cancer transformed growth and invasion, by activating Rac1→ERK and STAT3 signaling pathways, respectively. However, a key question is whether PKCι and PKCζ play redundant (or non-redundant) roles in pancreatic cancer cell transformed growth...
June 20, 2015: Oncotarget
Kelly K Y Seto, Irene L Andrulis
Ovarian cancer is one of the most aggressive gynaecological cancers, thus understanding the different biological pathways involved in ovarian cancer progression is important in identifying potential therapeutic targets for the disease. The aim of this study was to investigate the potential roles of Protein Kinase C Zeta (PRKCZ) in ovarian cancer. The atypical protein kinase C isoform, PRKCZ, is involved in the control of various signalling processes including cell proliferation, cell survival, and cell motility, all of which are important for cancer development and progression...
2015: PloS One
Sotiria Tsirmoula, Margarita Lamprou, Maria Hatziapostolou, Nelly Kieffer, Evangelia Papadimitriou
Pleiotrophin (PTN) is a heparin-binding growth factor that induces cell migration through binding to its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and integrin alpha v beta 3 (ανβ3). In the present work, we studied the effect of PTN on the generation of reactive oxygen species (ROS) in human endothelial cells and the involvement of ROS in PTN-induced cell migration. Exogenous PTN significantly increased ROS levels in a concentration and time-dependent manner in both human endothelial and prostate cancer cells, while knockdown of endogenous PTN expression in prostate cancer cells significantly down-regulated ROS production...
March 2015: Microvascular Research
Monika Höll, Rafal Koziel, Georg Schäfer, Haymo Pircher, Alexander Pauck, Martin Hermann, Helmut Klocker, Pidder Jansen-Dürr, Natalie Sampson
Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of male cancer death in Western nations. Thus, new treatment modalities are urgently needed. Elevated production of reactive oxygen species (ROS) by NADPH oxidase (Nox) enzymes is implicated in tumorigenesis of the prostate and other tissues. However, the identity of the Nox enzyme(s) involved in prostate carcinogenesis remains largely unknown. Analysis of radical prostatectomy tissue samples and benign and malignant prostate epithelial cell lines identified Nox5 as an abundantly expressed Nox isoform...
January 2016: Molecular Carcinogenesis
Markus A Queisser, Laura A Dada, Nimrod Deiss-Yehiely, Martin Angulo, Guofei Zhou, Fotini M Kouri, Lawrence M Knab, Jing Liu, Alexander H Stegh, Malcolm M DeCamp, G R Scott Budinger, Navdeep S Chandel, Aaron Ciechanover, Kazuhiro Iwai, Jacob I Sznajder
RATIONALE: Protein kinase C zeta (PKCζ) has been reported to act as a tumor suppressor. Deletion of PKCζ in experimental cancer models has been shown to increase tumor growth. However, the mechanisms of PKCζ down-regulation in cancerous cells have not been previously described. OBJECTIVES: To determine the molecular mechanisms that lead to decreased PKCζ expression and thus increased survival in cancer cells and tumor growth. METHODS: The levels of expression of heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), HOIL-1-interacting protein (HOIP), Shank-associated RH domain-interacting protein (SHARPIN), and PKCζ were analyzed by Western blot and/or quantitative real-time polymerase chain reaction in different cell lines...
September 15, 2014: American Journal of Respiratory and Critical Care Medicine
Ming-Hui Yang, Shyng-Shiou Yuan, Ying-Fong Huang, Po-Chiao Lin, Chi-Yu Lu, Tze-Wen Chung, Yu-Chang Tyan
Chitosan nanoparticle, a biocompatible material, was used as a potential drug delivery system widely. Our current investigation studies were the bioeffects of the chitosan nanoparticle uptake by liver cells. In this experiment, the characterizations of chitosan nanoparticles were measured by transmission electron microscopy and particle size analyzer. The average size of the chitosan nanoparticle was 224.6 ± 11.2 nm, and the average zeta potential was +14.08 ± 0.7 mV. Moreover, using proteomic approaches to analyze the differential protein expression patterns resulted from the chitosan nanoparticle uptaken by HepG2 and CCL-13 cells identified several proteins involved in the PI3K/AKT1/mTOR pathway...
2014: BioMed Research International
Yunfei Wen, Behrouz Zand, Bulent Ozpolat, Miroslaw J Szczepanski, Chunhua Lu, Erkan Yuca, Amy R Carroll, Neslihan Alpay, Chandra Bartholomeusz, Ibrahim Tekedereli, Yu Kang, Rajesha Rupaimoole, Chad V Pecot, Heather J Dalton, Anadulce Hernandez, Anna Lokshin, Susan K Lutgendorf, Jinsong Liu, Walter N Hittelman, Wen Y Chen, Gabriel Lopez-Berestein, Marta Szajnik, Naoto T Ueno, Robert L Coleman, Anil K Sood
Therapeutic upregulation of macroautophagy in cancer cells provides an alternative mechanism for cell death. Prolactin (PRL) and its receptor (PRLR) are considered attractive therapeutic targets because of their roles as growth factors in tumor growth and progression. We utilized G129R, an antagonist peptide of PRL, to block activity of the tumoral PRL/PRLR axis, which resulted in inhibition of tumor growth in orthotopic models of human ovarian cancer. Prolonged treatment with G129R induced the accumulation of redundant autolysosomes in 3D cancer spheroids, leading to a type II programmed cell death...
April 24, 2014: Cell Reports
Y Fang, H Shen, Y Cao, H Li, R Qin, Q Chen, L Long, X L Zhu, C J Xie, W L Xu
MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively...
January 2014: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Mostafa Saffari, Farshad H Shirazi, Mohammad Ali Oghabian, Hamid Reza Moghimi
The current methods for treatment of cancers are inadequate and more specific methods such as gene therapy are in progress. Among different vehicles, cationic liposomes are frequently used for delivery of genetic material. This investigation aims to prepare and optimize DOTAP cationic liposomes containing an antisense oligonuclotide (AsODN) against protein kinase C alpha in non-small cells lung cancer (NSCLC). To perform this investigation, two different methods of ethanol injection and thin film hydration were used to prepare AsODN-loaded DOTAP liposomes...
2013: Iranian Journal of Pharmaceutical Research: IJPR
Amanda M Butler, Michele L Scotti Buzhardt, Shuhua Li, Kristin E Smith, Alan P Fields, Nicole R Murray
Pancreatic cancer is a very aggressive disease with few therapeutic options. In this study, we investigate the role of protein kinase C zeta (PKCζ) in pancreatic cancer cells. PKCζ has been shown to act as either a tumor suppressor or tumor promoter depending upon the cellular context. We find that PKCζ expression is either maintained or elevated in primary human pancreatic tumors, but is never lost, consistent with PKCζ playing a promotive role in the pancreatic cancer phenotype. Genetic inhibition of PKCζ reduced adherent growth, cell survival and anchorage-independent growth of human pancreatic cancer cells in vitro...
2013: PloS One
Sze Ting Lee, Hong Ji, David W Greening, Robert W H Speirs, Angela Rigopoulos, Vinochani Pillay, Carmel Murone, Angela Vitali, Kai Stühler, Terrance G Johns, Georgia A Corner, John M Mariadason, Richard J Simpson, Andrew M Scott
An important mediator of tumorigenesis, the epidermal growth factor receptor (EGFR) is expressed in almost all non-transformed cell types, associated with tumor progression, angiogenesis and metastasis. The significance of the EGFR as a cancer therapeutic target is underscored by the clinical development of several different classes of EGFR antagonists, including monoclonal antibodies (mAb) and tyrosine kinase inhibitors. Extensive preclinical studies have demonstrated the anti-tumor effects of mAb806 against tumor xenografts overexpressing EGFR...
October 2013: Growth Factors
Ji Hae Kim, Jung Ok Lee, Soo Kyung Lee, Nami Kim, Ga Young You, Ji Wook Moon, Jie Sha, Su Jin Kim, Sun Hwa Park, Hyeon Soo Kim
Celastrol, an anti-oxidant flavonoid that is widely distributed in the plant kingdom, has been suggested to have chemopreventive effects on cancer cells: however, the mechanism of this process is not completely understood. In this study, we found that celastrol suppressed the viability of breast cancer MCF-7 cells in an AMP-activated protein kinase (AMPK)-dependent fashion. Celastrol also induced an increase in reactive oxygen species (ROS) levels, leading to AMPK phosphorylation. Protein kinase C (PKC) zeta was also shown to play a role in celastrol-induced ROS generation...
April 2013: Cellular Signalling
Hanna Lee, Minhee Park, Nara Shin, Gamin Kim, Yun Gi Kim, Jeon-Soo Shin, Hoguen Kim
High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct...
July 27, 2012: Biochemical and Biophysical Research Communications
S Yao, S J Ireland, A Bee, C Beesley, S S Forootan, A Dodson, T Dickinson, P Gerard, L-Y Lian, J M Risk, P Smith, M I Malki, Y Ke, C S Cooper, C Gosden, C S Foster
BACKGROUND: Previously, using gene-knockdown techniques together with genome expression array analysis, we showed the gene protein Kinase C (PKC)-zeta (PRKCZ) to mediate the malignant phenotype of human prostate cancer. However, according to NCBI, the gene has undergone several major iterations. Therefore, to understand the relationship between its structure and biological activities, we have analysed its expressed sequence in prostate cancer cell lines and tissues. METHODS: Transcriptome-walking and targeted PCR were used to sequence the mRNA transcribed from PRKCZ...
July 10, 2012: British Journal of Cancer
Andrew J Ewald, Robert J Huebner, Hildur Palsdottir, Jessie K Lee, Melissa J Perez, Danielle M Jorgens, Andrew N Tauscher, Kevin J Cheung, Zena Werb, Manfred Auer
Normal mammary morphogenesis involves transitions between simple and multilayered epithelial organizations. We used electron microscopy and molecular markers to determine whether intercellular junctions and apico-basal polarity were maintained in the multilayered epithelium. We found that multilayered elongating ducts had polarized apical and basal tissue surfaces both in three-dimensional culture and in vivo. However, individual cells were only polarized on surfaces in contact with the lumen or extracellular matrix...
June 1, 2012: Journal of Cell Science
Alessandro Rimessi, Erika Zecchini, Roberta Siviero, Carlotta Giorgi, Sara Leo, Rosario Rizzuto, Paolo Pinton
The atypical protein kinase C (PKC) isoform zeta (PKCζ) has been implicated in the intracellular transduction of mitogenic and apoptotic signals by acting on different signaling pathways. The key role of these processes in tumorigenesis suggests a possible involvement of PKCζ in this event. PKCζ is activated by cytotoxic treatments, inhibits apoptotic cell death and reduces the sensitivity of cancer cells to chemotherapeutic agents. Here, using pharmacological and DNA recombinant approaches, we show that oxidative stress triggers nuclear translocation of PKCζ and induces resistance to apoptotic agents...
March 1, 2012: Cell Cycle
Charles C Chu, Lu Zhang, Arjun Dhayalan, Briana M Agagnina, Amanda R Magli, Gia Fraher, Sebastien Didier, Linda P Johnson, William J Kennedy, Rajendra N Damle, Xiao-Jie Yan, Piers E M Patten, Saul Teichberg, Prasad Koduru, Jonathan E Kolitz, Steven L Allen, Kanti R Rai, Nicholas Chiorazzi
An infectious etiology has been proposed for many human cancers, but rarely have specific agents been identified. One difficulty has been the need to propagate cancer cells in vitro to produce the infectious agent in detectable quantity. We hypothesized that genome amplification from small numbers of cells could be adapted to circumvent this difficulty. A patient with concomitant chronic lymphocytic leukemia (CLL) and polycythemia vera (PV) requiring therapeutic phlebotomy donated a large amount of phlebotomized blood to test this possibility...
2011: Molecular Medicine
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