DOCSLIB.ORG

Plant Cell Biology: the Roots of Quiescence

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Plant Cell Biology: the Roots of Quiescence RESEARCH HIGHLIGHTS Confocal microscopy image PLANT CELL BIOLOGY of a root tip of Arabidopsis thaliana, showing quiescent centre cells (green fluorescence) surrounded The roots of quiescence by stem cells (within the white frame). Image courtesy of L. De Veylder, The growth and development of roots CCS52A2 is known to restrain QC cell Ghent University, Belgium. depend on the function of the root division, whereas the authors observed meristem, which has a well-defined low expression of ERF115 in QC cells. cellular organization: highly proliferative However, ERF115 mRNA levels stem cells surround a quiescent centre increased in conditions that promote (QC), comprised of a few cells that QC cell division, such as a modest only rarely divide. The QC is crucial for temperature rise or treatment maintaining the meristem as it controls with brassinosteroids, confirming the proliferation and differentiation of that it marks dividing QC cells. surrounding stem cells, and slow QC Importantly, a modified (dominant- self-renewal is central to these functions. negative) version of ERF115, unable De Veylder and colleagues now identify to activate transcription, prevented the ERF115 transcriptional activator as hyperproliferation of QC cells induced a rate-limiting factor of QC cell division. by brassinosteroids, indicating that ERF115 belongs to the ETHYLENE brassinosteroid-dependent QC division RESPONSE FACTOR family, members of at least partly depends on ERF115. This work suggests that QC which control the transcription of genes PHYTOSULFOKINE PRECURSOR 5 proliferation depends on the levels CCS52A2 involved in growth and development. (PSK5) — which encodes a peptide of ERF115, on which the APC/C ERF115 was identified in a screen hormone that controls root growth and brassinosteroids have antagonistic for proteins that bind to an activating and cell proliferation — was identified effects. In addition, the authors subunit of the APC/C (anaphase as a target of ERF115. Consistently, suggest that ERF115-dependent QC promoting complex; also known as both overexpression and stabilization proliferation replenishes surrounding the cyclosome) — CCS52A2 (CELL of ERF115 (through mutation of stem cells upon damage, thereby CYCLE SWITCH PROTEIN 52 A2) — APC/‌CCCS52A2) led to increased PSK5 contributing to the longevity of the that promotes QC cell proliferation transcript levels. Furthermore, in the stem cell niche. when ectopically expressed in absence of a functional receptor for PSK Kim Baumann Arabidopsis thaliana. APC/C targets peptides, overexpression of ERF115 was ORIGINAL RESEARCH PAPER Heyman, J. et al. cell cycle proteins for degradation, and unable to induce QC proliferation, which ERF115 controls root quiescent center cell division biochemical data confirmed that ERF115 indicats that ERF115-dependent QC and stem cell replenishment. Science http//dx.doi. org/10.1126/science.1240667 (2013) is an APC/CCCS52A2 target. proliferation depends on PSK signalling. NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 14 | DECEMBER 2013 | 1 © 2013 Macmillan Publishers Limited. All rights reserved.
Load more

Recommended publications
  • Mir-451A Suppresses Cell Proliferation, Metastasis and EMT Via Targeting YWHAZ in Hepatocellular Carcinoma
    European Review for Medical and Pharmacological Sciences 2019; 23: 5158-5167 MiR-451a suppresses cell proliferation, metastasis and EMT via targeting YWHAZ in hepatocellular carcinoma G.-Y. WEI1, M. HU2, L. ZHAO1, W.-S. GUO1 1Department of General Surgery, Henan Traditional Chinese Medicine Hospital, Zhengzhou, China 2Department of Infection Management, Henan Traditional Chinese Medicine Hospital, Zhengzhou, China Abstract. – OBJECTIVE: MicroRNAs (miR- lines. Moreover, miR-451a inhibited the prolif- NAs) have been identified to participate in eration, invasion and migration of HCC cells via the progression of hepatocellular carcinoma targeting YWHAZ. Our findings indicated that (HCC). However, the function of miR-451a in miR-451a could serve as a novel target for HCC HCC remains unknown. The aim of this study diagnosis and biological therapy. was to determine the function of miR-451a by construction of several experiments in HCC tis- Key Words: sues and cells. MiR-451a, Hepatocellular carcinoma (HCC), Prolifer- PATIENTS AND METHODS: The expression ation, Metastasis, YWHAZ. level of miR-451a in 69 paired of HCC and ad- jacent normal tissue samples was detected us- ing quantitative Real-time polymerase chain re- Introduction action (qRT-PCR). MiR-451a expression in HCC derived cell lines was detected as well. By trans- fecting with miR-451a mimics or inhibitor, the Hepatocellular carcinoma (HCC) accounts expression level of miR-451a in HepG2 or Huh-7 for 85-90% of primary liver cancer. HCC is the cells was up- or down-regulated. MTT (3-(4,5-di- fifth most common morbidity and third most methylthiazol-2-yl)-2,5-diphenyl tetrazolium bro- common mortality cancer worldwide1.
    [Show full text]
  • Akt Is Involved in the Inhibition of Cell Proliferation by EGF
    EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 39, No. 4, 491-498, August 2007 Akt is involved in the inhibition of cell proliferation by EGF Soung Hoo Jeon1, Woo-Jeong Jeong1, proliferation and embryonic axis formation (Zeng et Jae-Young Cho1, Kee-Ho Lee2 al., 1997). Axin is a multi-domain scaffold protein and Kang-Yell Choi1,3 that associates directly with β-catenin, GSK3β, and phosphatase PP2A (Hsu et al., 1999). Axin is 1 implicated in down-regulation of Wnt/β-catenin Department of Biotechnology signaling (Ikeda et al., 1998; Itoh et al., 1998; Yonsei University Sakanaka et al., 1998; Kikuchi et al., 2006). There Seoul 120-752, Korea 2 are two vertebrate Axins (Axin 1 and Axin 2). Axin1 Laboratory of Molecular Oncology is constitutively expressed, but Axin 2 is induced Korea Institute of Radiological and Medical Sciences by active Wnt signaling and acts therefore in a Seoul 139-706, Korea negative feedback loop (Yan et al., 2001; Jho et 3 Corresponding author: Tel, 82-2-2123-2887; al., 2002; Lustig et al., 2002). Overexpressed Axin Fax, 82-2-362-7265; E-mail, [email protected] destabilizes β-catenin (Behrens et al., 1998; Hart et al., 1998; Ikeda et al.,1998; Kishida et al., 1998; Accepted 28 May 2007 Nakamura et al., 1998; Sakanaka et al., 1998; Yamamoto et al., 1998). Loss of Axin results in nu- Abbreviations: APC, adenomatos polyposis coli; BrdU, bromode- clear accumulation of β-catenin followed by forma- oxyuridine; DAPI, 4'6-diamidino-2-phenylindole; PI3K, phosphatidyl tion of the β-catenin-TCF transcriptional complex inositol 3-kinase involving transcriptional activation of its target genes (Sakanaka et al., 1998).
    [Show full text]
  • Dedifferentiation, Transdifferentiation, and Reprogramming: Future Directions in Regenerative Medicine
    82 Dedifferentiation, Transdifferentiation, and Reprogramming: Future Directions in Regenerative Medicine Cristina Eguizabal, PhD1 Nuria Montserrat, PhD1 Anna Veiga, PhD1,2 Juan Carlos Izpisua Belmonte, PhD1,3 1 Center for Regenerative Medicine in Barcelona Address for correspondence and reprint requests Juan Carlos Izpisua 2 Reproductive Medicine Service, Institut Universitari Dexeus, Belmonte, PhD, Gene Expression Laboratory, The Salk Institute for Barcelona, Spain Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 93027 3 Gene Expression Laboratory, The Salk Institute for Biological Studies, (e-mail: [email protected]). La Jolla, California Semin Reprod Med 2013;31:82–94 Abstract The main goal of regenerative medicine is to replace damaged tissue. To do this it is Keywords necessary to understand in detail the whole regeneration process including differenti- ► regenerative ated cells that can be converted into progenitor cells (dedifferentiation), cells that can medicine switch into another cell type (transdifferentiation), and somatic cells that can be ► stem cells induced to become pluripotent cells (reprogramming). By studying the regenerative ► dedifferentiation processes in both nonmammal and mammal models, natural or artificial processes ► transdifferentiation could underscore the molecular and cellular mechanisms behind these phenomena and ► reprogramming be used to create future regenerative strategies for humans. To understand any regenerative system, it is crucial to find the potency and differentiate and how they can revert to pluri- cellular origins of renewed tissues. Using techniques like potency (reprogramming) or switch lineages (dedifferentia- genetic lineage tracing and single-cell transplantation helps tion and transdifferentiation). to identify the route of regenerative sources. These tools were We synthesize the studies of different model systems to developed first in nonmammal models (flies, amphibians, and highlight recent insights that are integrating the field.
    [Show full text]
  • Lncrna SNHG14 Promotes the Progression of Cervical Cancer By
    Pathology - Research and Practice 215 (2019) 668–675 Contents lists available at ScienceDirect Pathology - Research and Practice journal homepage: www.elsevier.com/locate/prp LncRNA SNHG14 promotes the progression of cervical cancer by regulating miR-206/YWHAZ T ⁎ Nannan Jia, , Yuhuan Wanga, Guangli Baob, Juanli Yanb, Sha Jic a Shihezi University, Shihezi, Xinjiang 832000, China b The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang 832000, China c Xinjiang Municipal People’s Hospital, Urumqi, Xinjiang 830001, China ARTICLE INFO ABSTRACT Keywords: Accumulating evidence suggests that lncRNAs play key roles in many cancers. It has been reported that long SNHG14 non‐coding RNA SNHG14 promotes cell proliferation and metastasis in multiple cancers. However, the role and miR-206 underlying molecular mechanism of SNHG14 in cervical cancer (CC) remain largely unclear. In this study, we YWHAZ discovered that the relative expression of SNHG14 was significantly upregulated in CC tissues and cells, and CC associated with the overall survival of CC patients. Moreover, knockdown of SNHG14 significantly inhibited cell Progression proliferation, migration and invasion, and promoted cell apoptosis in CC. Molecular mechanism explorations revealed that SNHG14 acted as a sponge of miR-206 and that YWHAZ was a downstream target gene of miR-206 in CC. Spearman’s correlation analysis uncovered a significantly negative correlation between SNHG14 (or YWHAZ) and miR-206 expression, while a significantly positive correlation between SNHG14 and YWHAZ ex- pression in CC tissues. We also found that the effect of SNHG14 knockdown on the CC progression could be partly rescued by overexpression of YWHAZ at the same time.
    [Show full text]
  • Overexpression of YWHAZ Relates to Tumor Cell Proliferation and Malignant Outcome of Gastric Carcinoma
    FULL PAPER British Journal of Cancer (2013) 108, 1324–1331 | doi: 10.1038/bjc.2013.65 Keywords: YWHAZ (14-3-3z); gastric carcinoma; malignant outcome; prognostic factor Overexpression of YWHAZ relates to tumor cell proliferation and malignant outcome of gastric carcinoma Y Nishimura1,3, S Komatsu1,3, D Ichikawa1, H Nagata1, S Hirajima1, H Takeshita1, T Kawaguchi1, T Arita1, H Konishi1, K Kashimoto1, A Shiozaki1, H Fujiwara1, K Okamoto1, H Tsuda2 and E Otsuji1 1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan and 2Department of Pathology, National Cancer Center Hospital, Tokyo, Japan Background: Several studies have demonstrated that YWHAZ (14-3-3z), included in the 14-3-3 family of proteins, has been implicated in the initiation and progression of cancers. We tested whether YWHAZ acted as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). Methods: We analysed 7 GC cell lines and 141 primary tumours, which were curatively resected in our hospital between 2001 and 2003. Results: Overexpression of the YWHAZ protein was frequently detected in GC cell lines (six out of seven lines, 85.7%) and primary tumour samples of GC (72 out of 141 cases, 51%), and significantly correlated with larger tumour size, venous and lymphatic invasion, deeper tumour depth, and higher pathological stage and recurrence rate. Patients with YWHAZ-overexpressing tumours had worse overall survival rates than those with non-expressing tumours in both intensity and proportion expression-dependent manner. YWHAZ positivity was independently associated with a worse outcome in multivariate analysis (P ¼ 0.0491, hazard ratio 2.3 (1.003–5.304)).
    [Show full text]
  • A Novel Function of YWHAZ/B-Catenin Axis in Promoting Epithelial–Mesenchymal Transition and Lung Cancer Metastasis
    Published OnlineFirst August 21, 2012; DOI: 10.1158/1541-7786.MCR-12-0189 Molecular Cancer Angiogenesis, Metastasis, and the Cellular Microenvironment Research A Novel Function of YWHAZ/b-Catenin Axis in Promoting Epithelial–Mesenchymal Transition and Lung Cancer Metastasis Ching-Hsien Chen1,4, Show-Mei Chuang1, Meng-Fang Yang1, Jiunn-Wang Liao2, Sung-Liang Yu4, and Jeremy J.W. Chen1,3 Abstract YWHAZ, also known as 14-3-3zeta, has been reportedly elevated in many human tumors, including non–small cell lung carcinoma (NSCLC) but little is known about its specific contribution to lung cancer malignancy. Through a combined array-based comparative genomic hybridization and expression microarray analysis, we identified YWHAZ as a potential metastasis enhancer in lung cancer. Ectopic expression of YWHAZ on low invasive cancer cells showed enhanced cell invasion, migration in vitro, and both the tumorigenic and metastatic potentials in vivo. Gene array analysis has indicated these changes associated with an elevation of pathways relevant to epithelial–mesenchymal transition (EMT), with an increase of cell protrusions and branchings. Conversely, knockdown of YWHAZ levels with siRNA or short hairpin RNA (shRNA) in invasive cancer cells led to a reversal of EMT. We observed that high levels of YWHAZ protein are capable of activating b-catenin–mediated transcription by facilitating the accumulation of b-catenin in cytosol and nucleus. Coimmunoprecipitation assays showed a decrease of ubiquitinated b-catenin in presence of the interaction between YWHAZ and b-catenin. This interaction resulted in disassociating b-catenin from the binding of b-TrCP leading to increase b-catenin stability. Using enforced expression of dominant-negative and -positive b-catenin mutants, we confirmed that S552 phosphorylation of b-catenin increases the b-catenin/YWHAZ complex formation, which is important in pro- moting cell invasiveness and the suppression of ubiquitnated b-catenin.
    [Show full text]
  • Increasing Antiproliferative Properties of Endocannabinoids in N1E-115 Neuroblastoma Cells Through Inhibition of Their Metabolism
    Increasing Antiproliferative Properties of Endocannabinoids in N1E-115 Neuroblastoma Cells through Inhibition of Their Metabolism Laurie Hamtiaux1, Laurie Hansoulle1, Nicolas Dauguet2, Giulio G. Muccioli3, Bernard Gallez4, Didier M. Lambert1* 1 Medicinal Chemistry, Cannabinoid and Endocannabinoid Research Group, Louvain Drug Research Institute, Universite´ Catholique de Louvain, Brussels, Belgium, 2 de Duve Institute, Universite´ Catholique de Louvain, Brussels, Belgium, 3 Bioanalysis and Pharmacology of Bioactive Lipids Laboratory, Louvain Drug Research Institute, Universite´ Catholique de Louvain, Brussels, Belgium, 4 Biomedical Magnetic Resonance, Louvain Drug Research Institute, Universite´ Catholique de Louvain, Brussels, Belgium Abstract The antitumoral properties of endocannabinoids received a particular attention these last few years. Indeed, these endogenous molecules have been reported to exert cytostatic, apoptotic and antiangiogenic effects in different tumor cell lines and tumor xenografts. Therefore, we investigated the cytotoxicity of three N-acylethanolamines – N-arachidonoy- lethanolamine (anandamide, AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA) - which were all able to time- and dose-dependently reduce the viability of murine N1E-115 neuroblastoma cells. Moreover, several inhibitors of FAAH and NAAA, whose presence was confirmed by RT-PCR in the cell line, induced cell cytotoxicity and favored the decrease in cell viability caused by N-acylethanolamines. The most cytotoxic treatment was achieved by the co-incubation of AEA with the selective FAAH inhibitor URB597, which drastically reduced cell viability partly by inhibiting AEA hydrolysis and consequently increasing AEA levels. This combination of molecules synergistically decreased cell proliferation without inducing cell apoptosis or necrosis. We found that these effects are independent of cannabinoid, TRPV1, PPARa, PPARc or GPR55 receptors activation but seem to occur through a lipid raft-dependent mechanism.
    [Show full text]
  • Phorbol Ester Stimulates Ethanolamine Release from the Metastatic Basal Prostate Cancer Cell Line PC3 but Not from Prostate Epithelial Cell Lines Lncap and P4E6
    FULL PAPER British Journal of Cancer (2014) 111, 1646–1656 | doi: 10.1038/bjc.2014.457 Keywords: Etn phosphoglycerides; phorbol ester; protein kinase C; ethanolamine; prostate cancer epithelial cell lines; phospholipase D Phorbol ester stimulates ethanolamine release from the metastatic basal prostate cancer cell line PC3 but not from prostate epithelial cell lines LNCaP and P4E6 J Schmitt1, A Noble1,2, M Otsuka1, P Berry1,2, N J Maitland1,2 and M G Rumsby*,1 1Department of Biology, University of York, York, YO10 5DD, UK and 2Yorkshire Cancer Research Laboratory, University of York, York YO10 5DD, UK Background: Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethanolamine (Etn) metabolites released to the medium. Methods: Prostate epithelial cell lines P4E6, LNCaP and PC3 were models of prostate cancer (PCa). PNT2C2 and PNT1A were models of benign prostate epithelia. Cellular EtnPGs were labelled with [1-3H]-Etn hydrochloride. PKC was activated with phorbol ester (TPA) and inhibited with Ro31-8220 and GF109203X. D609 was used to inhibit PLD (phospholipase D). [3H]-labelled Etn metabolites were resolved by ion-exchange chromatography. Sodium oleate and mastoparan were tested as activators of PLD2. Phospholipase D activity was measured by a transphosphatidylation reaction. Cells were treated with ionomycin to raise intracellular Ca2 þ levels. Results: Unstimulated cell lines release mainly Etn and glycerylphosphorylEtn (GPEtn) to the medium. Phorbol ester treatment over 3h increased Etn metabolite release from the metastatic PC3 cell line and the benign cell lines PNT2C2 and PNT1A but not from the tumour-derived cell lines P4E6 and LNCaP; this effect was blocked by Ro31-8220 and GF109203X as well as by D609, which inhibited PLD in a transphosphatidylation reaction.
    [Show full text]
  • Deformable Cell Model of Tissue Growth
    computation Article Deformable Cell Model of Tissue Growth Nikolai Bessonov 1 and Vitaly Volpert 2,* 1 Institute of Problems of Mechanical Engineering, Russian Academy of Sciences, 199178 Saint Petersburg, Russia; [email protected] 2 Institut Camille Jordan, UMR 5208 CNRS, University Lyon 1, 69622 Villeurbanne, France * Correspondence: [email protected]; Tel.: +3-347-243-2765 Received: 30 September 2017; Accepted: 24 October 2017; Published: 30 October 2017 Abstract: This paper is devoted to modelling tissue growth with a deformable cell model. Each cell represents a polygon with particles located at its vertices. Stretching, bending and pressure forces act on particles and determine their displacement. Pressure-dependent cell proliferation is considered. Various patterns of growing tissue are observed. An application of the model to tissue regeneration is illustrated. Approximate analytical models of tissue growth are developed. Keywords: deformable cells; tissue growth; pattern formation; analytical approximation 1. Introduction Mathematical and computer modelling of tissue growth is used in various biological problems such as wound healing and regeneration, morphogenesis, tumor growth, etc. Tissue growth can be described with continuous models: partial differentiation equations for cell concentrations (reaction–diffusion equations), Navier–Stokes or Darcy equations for the velocity of the medium, and elasticity equations for the distribution of mechanical stresses. There is a vast literature devoted to these models (see, e.g., [1–5] and references therein). Another approach deals with individual-based models where cells are considered as individual objects. It allows a more detailed description at the level of individual cells though analytical investigation of such models becomes impossible and their numerical simulations are often more involved than for the continuous models.
    [Show full text]
  • The P38 Pathway: from Biology to Cancer Therapy
    International Journal of Molecular Sciences Review The p38 Pathway: From Biology to Cancer Therapy 1,2, 1,2, 1,2, 1,2, Adrián Martínez-Limón y, Manel Joaquin y, María Caballero y , Francesc Posas * and Eulàlia de Nadal 1,2,* 1 Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain; [email protected] (A.M.-L.); [email protected] (M.J.); [email protected] (M.C.) 2 Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), E-08003 Barcelona, Spain * Correspondence: [email protected] (F.P.); [email protected] (E.d.N.); Tel.: +34-93-403-4810 (F.P.); +34-93-403-9895 (E.d.N.) These authors contributed equally to this work. y Received: 29 January 2020; Accepted: 9 March 2020; Published: 11 March 2020 Abstract: The p38 MAPK pathway is well known for its role in transducing stress signals from the environment. Many key players and regulatory mechanisms of this signaling cascade have been described to some extent. Nevertheless, p38 participates in a broad range of cellular activities, for many of which detailed molecular pictures are still lacking. Originally described as a tumor-suppressor kinase for its inhibitory role in RAS-dependent transformation, p38 can also function as a tumor promoter, as demonstrated by extensive experimental data. This finding has prompted the development of specific inhibitors that have been used in clinical trials to treat several human malignancies, although without much success to date. However, elucidating critical aspects of p38 biology, such as isoform-specific functions or its apparent dual nature during tumorigenesis, might open up new possibilities for therapy with unexpected potential.
    [Show full text]
  • Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of Mir-30C-5P and Mir-30C-2-3P Regulation on Oncogenic Genes
    cancers Article Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes Takako Tanaka 1 , Reona Okada 2, Yuto Hozaka 1 , Masumi Wada 1, Shogo Moriya 3, Souichi Satake 1, Tetsuya Idichi 1, Hiroshi Kurahara 1, Takao Ohtsuka 1 and Naohiko Seki 2,* 1 Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan; [email protected] (T.T.); [email protected] (Y.H.); [email protected] (M.W.); [email protected] (S.S.); [email protected] (T.I.); [email protected] (H.K.); [email protected] (T.O.) 2 Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; [email protected] 3 Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-43-226-2971; Fax: +81-43-227-3442 Received: 4 August 2020; Accepted: 21 September 2020; Published: 23 September 2020 Simple Summary: A total of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were identified as tumor suppressive miR-30c-5p and miR-30c-2-3p targets in pancreatic ductal adenocarcinoma (PDAC), and expression of these genes were independent prognostic factors for patient survival. Furthermore, aberrant expression of TOP2A and its transcriptional activators (SP1 and HMGB2) enhanced malignant transformation of PDAC cells. Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, and its prognosis is abysmal; only 25% of patients survive one year, and 5% live for five years.
    [Show full text]
  • Tumor Suppressors Having Oncogenic Functions: the Double Agents
    cells Review Tumor Suppressors Having Oncogenic Functions: The Double Agents Neerajana Datta 1, Shrabastee Chakraborty 1, Malini Basu 2 and Mrinal K. Ghosh 1,* 1 Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector–V, Salt Lake, Kolkata-700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India; [email protected] (N.D.); [email protected] (S.C.) 2 Department of Microbiology, Dhruba Chand Halder College, Dakshin Barasat, South 24 Paraganas, West Bengal PIN-743372, India; [email protected] * Correspondence: [email protected] Abstract: Cancer progression involves multiple genetic and epigenetic events, which involve gain-of- functions of oncogenes and loss-of-functions of tumor suppressor genes. Classical tumor suppressor genes are recessive in nature, anti-proliferative, and frequently found inactivated or mutated in cancers. However, extensive research over the last few years have elucidated that certain tumor suppressor genes do not conform to these standard definitions and might act as “double agents”, playing contrasting roles in vivo in cells, where either due to haploinsufficiency, epigenetic hyperme- thylation, or due to involvement with multiple genetic and oncogenic events, they play an enhanced proliferative role and facilitate the pathogenesis of cancer. This review discusses and highlights some of these exceptions; the genetic events, cellular contexts, and mechanisms by which four important tumor suppressors—pRb, PTEN, FOXO, and PML display their oncogenic potentials and pro-survival traits in cancer. Keywords: tumor suppressor genes; Rb; PTEN; FOXO; PML; cancer Citation: Datta, N.; Chakraborty, S.; Basu, M.; Ghosh, M.K.
    [Show full text]