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Protein kinase C zeta and cancer

Ravi Kiran Deevi, Arman Javadi, Jane McClements, Jekaterina Vohhodina, Kienan Savage, Maurice Bernard Loughrey, Emma Evergren, Frederick Charles Campbell
Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring...
March 9, 2018: Journal of Pathology
Omar M Rahal, Adam R Wolfe, Pijus K Mandal, Richard Larson, Sanda Tin, Cristina Jimenez, Dadong Zhang, Janet Horton, James M Reuben, John S McMurray, Wendy A Woodward
PURPOSE: To determine the role of macrophage polarization on the response of inflammatory breast cancer (IBC) cells to radiation and whether modulation of macrophage plasticity can alter radiation response. METHODS AND MATERIALS: The human THP-1 monocyte cell line and primary human monocytes isolated from peripheral blood mononuclear cells were differentiated into macrophages and polarized to either an "antitumor" (M1) or a "protumor" (M2) phenotype...
March 15, 2018: International Journal of Radiation Oncology, Biology, Physics
Min-Kyung Yeo, Ji Yeon Kim, In-Ock Seong, Jin-Man Kim, Kyung-Hee Kim
Background: Protein kinase C zeta/lambda (PKCζ/λ) is a family of protein kinase enzymes that contributes to cell proliferation and regulation, which are important for cancer development. PKCζ/λ has been shown to be an important regulator of tumorigenesis in intestinal cancer. The phosphorylated form of PKCζ/λ, p-PKCζ/λ, is suggested as an active form of PKCζ/λ. However, p-PKCζ/λ expression and its clinicopathologic implication in colorectal adenocarcinoma (CRAC) are unclear. Methods: Seven whole-tissue sections of malignant polyps containing both non-neoplastic and neoplastic mucosa, 11 adenomas with low-grade dysplasia, and 173 CRACs were examined by immunohistochemistry and western blot assay for p-PKCζ/λ protein expression...
2017: Journal of Cancer
Wishrawana S Ratnayake, André H Apostolatos, David A Ostrov, Mildred Acevedo-Duncan
Atypical protein kinase Cs (aPKC) are involved in cell cycle progression, tumorigenesis, cell survival and migration in many cancers. We believe that aPKCs play an important role in cell motility of melanoma by regulating cell signaling pathways and inducing epithelial to mesenchymal transition (EMT). We have investigated the effects of two novel aPKC inhibitors; 2-acetyl-1,3-cyclopentanedione (ACPD) and 3,4-diaminonaphthalene-2,7-disulfonic acid (DNDA) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocytes...
September 22, 2017: International Journal of Oncology
Hui-Hui Fan, Ling Li, Yu-Ming Zhang, Jie Yang, Mao-Cheng Li, Fang-Yin Zeng, Fan Deng
Tumor-associated macrophages are key regulators of the complex interplay between tumor and tumor microenvironment. M2 Macrophages, one type of tumor-associated macrophages, are involved in prostate cancer growth and progression. Protein kinase C zeta has been shown to suppress prostate cancer cell growth, invasion, and metastasis as a tumor suppressor; however, its role in chemotaxis and activation of tumor-associated macrophages remains unclear. Here, we investigated the role of protein kinase C zeta of prostate cancer cells in regulation of macrophage chemotaxis and M2 phenotype activation...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Li Cheng, Youqun Ke, Shuisheng Yu, Juehua Jing
To explore a novel combination of chemotherapy, gene therapy, and thermotherapy for osteosarcoma, a targeted heat-sensitive co-delivery system based on bacterial magnetosomes (BMs) was developed. The optimal culture conditions of magnetotactic bacteria (MTB) AMB-1 and characterization of BMs were achieved. A recombinant eukaryotic plasmid heat shock protein 70-polo-like kinase 1-short hairpin RNA (pHSP70-Plk1-shRNA) under transcriptional control of a thermosensitive promoter (human HSP70 promoter) was constructed for gene therapy...
2016: International Journal of Nanomedicine
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)...
August 2, 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
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