This paper describes the inner workings of centrioles (a pair of small organelles adjacent to the nucleus) as they create cell electropolarity, engage in cell division (mitosis), but in going awry, also promote the development of cancers. The electropolarity arises from vibrations of microtubules composing the centrioles. Mitosis begins as each centrioles duplicates itself by growing a daughter centriole on its side. If during duplication more than one daughter is grown, cancer can occur and the cells divide uncontrollably. Cancer cells with supernumerary centrioles have high electropolarity which can serve as an attractor for charged therapeutic nanoparticles.
Issue Section:
Research Papers
Topics:
Cancer,
Electromagnetism,
Geometry,
Vibration,
Nanoparticles,
Cylinders,
Proteins,
Biomedicine,
Biotechnology
References
1.
Boveri
, T.
, 1929
, The Origin of Malignant Tumors
, Williams and Wilkins
, Baltimore, MD
.2.
Marx
, J.
, 2001
, “Do Centrosome Abnormalities Lead to Cancer?
,” Science
, 292
(5516
), pp. 426
–429
.10.1126/science.292.5516.4263.
Kramer
, A.
, Neben
, K.
, and Ho
, A. D.
, 2002
, “Centrosome Replication, Genomic Instability and Cancer
,” Leukemia
, 16
(5
), pp. 767
–775
.10.1038/sj.leu.24024544.
Loffler
, H.
, Lukas
, J.
, Bartek
, J.
, and Kramer
, A.
, 2006
, “Structure Meets Function–Centrosomes, Genome Maintenance and the DNA Damage Response
,” Exp. Cell Res.
, 312
(14
), pp. 2633
–2640
.10.1016/j.yexcr.2006.06.0085.
Luders
, J.
, and Stearns
, T.
, 2007
, “Microtubule-Organizing Centres: A Re-Evaluation
,” Nature Rev. Mol. Cell Biol.
, 8
(2), pp. 161
–167
.10.1038/nrm21006.
Bettencourt-Dias
, M.
, and Glover
, D.
, 2007
, “Centrosome Biogenesis and Function: Centrosomics Brings New Understanding
,” Nat. Rev. Mol. Cell Biol.
, 8
(6), pp. 451
–463
.10.1038/nrm21807.
Kwon
, M.
, Godinho
, S. A.
, Chandhok
, N. S.
, Ganem
, N. J.
, Azioune
, A.
, Thery
, M.
, and Pellman
, D.
, 2008
, “Mechanisms to Suppress Multiplanar Divisions in Cancer Cells With Extra Chromosomes
,” Genes Dev.
, 22
(16
), pp. 2189
–2203
.10.1101/gad.17009088.
Schafer
, P. W.
, 1969
, “Centrioles of a Human Cancer: Intercellular Order and Intracellular Disorder
,” Science
, 164
(3885
), pp. 1300
–1303
.10.1126/science.164.3885.13009.
Schafer
, P. W.
, and Chandler
, J. A.
, 1970
, “Electron Probe X-Ray Microanalysis of a Normal Centriole
,” Science
, 170
(3963
), pp. 1204
–1209
.10.1126/science.170.3963.120410.
Schafer
, P. W.
, 1975
, “Centrioles: Intercellular Order in Normal and Malignant Cells
,” J. Thoracic Cardiovasc. Surg.
, 63
(3
), pp. 472
–477
.11.
Wang
, F.
, Pauletti
, G. M.
, Wang
, J.
, Zhang
, J.
, Ewing
, R. C.
, Wang
, Y.
, and Shi
, D.
, 2013
, “Dual Surface-Functionalized Janus Nanocomposites of Polystyrene/Fe3O4@SiO2 for Simultaneous Tumor Cell Targeting and Stimulus-Induced Drug Release
,” Adv. Mater.
, 25
(25
), pp. 3485
–3489
.10.1002/adma.20130137612.
Alberts
, B.
, Bray
, D.
, Lewis
, J.
, Raff
, M.
, Roberts
, K.
, and Watson
, J. D.
, 1994
, Molecular Biology of the Cell
, 3rd ed., Garland Publishing
, New York
, pp. 803
–818
.13.
Lange
, B. M. H.
, and Gull
, K.
, 1996
, “Structure and Function of the Centriole in Animal Cells: Progress and Questions
,” Trends Cell Biol.
, 6
(9
), pp. 348
–352
.10.1016/0962-8924(96)10033-714.
Portet
, W.
, Tuszynski
, J. A.
, Hogue
, C. W. V.
, and Dixon
, J. M.
, 2005
, “Elastic Vibrations in Seamless Microtubules
,” Eur. Biophys. J.
, 34
(7
), pp. 912
–920
.10.1007/s00249-005-0461-415.
Qian
, X. S.
, Zhang
, J. Q.
, and Ru
, C. Q.
, 2007
, “Wave Propagation in Orthotropic Microtubules
,” J. Appl. Phys.
, 101
(8
), p. 084702
10.1063/1.271757316.
Doxey
, S.
, 2001
, “Re-Evaluating Centrosome Function
,” Nat. Rev. Mol. Cell Biol.
, 2
(9), pp. 688
–689
.10.1038/3508957517.
Azimzadeh
, J.
, and Bornens
, M.
, 2007
, “Structure and Duplication of the Centrosome
,” J. Cell Sci.
, 120
(13
), pp. 2139
–2142
.10.1242/jcs.00523118.
Bornens
, M.
, 2012
, “The Centrosome in Cells and Organisms
,” Science
, 335
(6067
), pp. 422
–425
.10.1126/science.120903719.
Tassin
, A.-M.
, and Bornens
, M.
, 1999
, “Centrosome Structure and Microtubules Nucleation in Animal Cells
,” Biol. Cell
, 91
(4–5
), pp. 343
–354
.10.1111/j.1768-322X.1999.tb01092.x20.
Becker
, W. M.
, 1986
, The World of the Cell
, Benjamin Cummings Publishing Co.
, Menlo Park, CA
, pp. 464
–468
.21.
Kleyleon-Sohn
, J.
, Westendorf
, J.
, Clech
, M. L.
, Hobedauck
, R.
, Stierhot
, Y.
, and Nigg
, E. A.
, 2007
, “Plk4-Induced Centriole Biogenesis in Human Cells
,” Dev. Cell
, 13
(2
), pp. 190
–202
.10.1016/j.devcel.2007.07.00222.
Nigg
, E. A.
, 2008
, “Centrosome Duplication: Of Rules and Licenses
,” Trends Cell Biol.
, 17
(5
), pp. 215
–221
.10.1016/j.tcb.2007.03.00323.
Strand
, P.
, and Gonczy
, P.
, 2008
, “Mechanisms of Procentriole Formation
,” Trends Cell Biol.
, 18
(8
), pp. 389
–396
.10.1016/j.tcb.2008.06.00424.
McKean
, P. G.
, Vaughan
, S.
, and Gull
, K.
, 2001
, “The Extended Tubulin Superfamily
,” J. Cell Sci.
, 144
(15), pp. 2723
–2733
.25.
Pokorny
, J.
, Hasek
, J.
, and Jelinek
, F.
, 2005
, “Electromagnetic Field of Microtubules: Effects on Transfer of Mass Particles and Electrons
,” J. Biol. Phys.
, 31
(3–4
), pp. 501
–514
.10.1007/s10867-005-1286-126.
Pokorny
, J.
, Hasek
, J.
, and Jelinek
, F.
, 2005
, “Endogenous Electric Field and Organization of Living Matter
,” Electromagn. Biol. Med.
, 24
(3
), pp. 183
–197
.10.1080/1536837050037956627.
Tsai
, M.-C.
, and Ahringer
, J.
, 2007
, “Microtubules are Involved in Anterior-Posterior Axis Formation in C.elegans Embryos
,” J. Cell Biol.
, 179
(3
), pp. 397
–402
.10.1083/jcb.20070810128.
Cifra
, M.
, Pokorny
, J.
, Havelka
, D.
, and Kucera
, O.
, 2010
, “Electric Field Generated by Axial Longitudinal Vibration Modes of Microtubule
,” Biosystems
, 100
(2
), pp. 122
–131
.10.1016/j.biosystems.2010.02.00729.
Pokorny
, J.
, 2011
, “Electrodynamic Activity of Healthy and Cancer Cells
,” J. Phys.: Conf. Ser.
329
, p. 012007
.10.1088/1742-6596/329/1/01200730.
Werner
, M. E.
, Hwang
, P.
, Huisman
, F.
, Taborek
, P.
, Yu
, C. C.
, and Mitchell
, B. J.
, 2011
, “Actin and Microtubules Drive Differential Aspects of Planar Cell Polarity in Multiciliated Cells
,” J. Cell Biol.
, 195
(1
), pp. 19
–26
.10.1083/jcb.20110611031.
Nigg
, E. A.
, and Stearns
, T.
, 2011
, “The Centrosome Cycle: Centriole Biogenesis, Duplication and Inherent Asymmetries
,” Nat. Cell Biol.
, 13
(10
), pp. 1154
–1160
.10.1038/ncb234532.
Dutcher
, S. K.
, 2001
, “The Tubulin Family: Alpha to Eta
,” Curr. Opin. Cell Biol.
, 13
(1
), pp. 49
–54
.10.1016/S0955-0674(00)00173-333.
Mahen
, R.
, and Venkitaraman
, A. R.
, 2012
, “Pattern Formation in Centrosome Assembly
,” Curr. Opin. Cell Biol.
, 24
(1), pp. 19
–23
.10.1016/j.ceb.2011.12.01234.
Beisson
, J.
, and Jerka-Dziadesz
, M.
, 1999
, “Polarities of the Centriolar Structure: Morphogenetic Consequences
,” Biol. Cell
, 91
(4–5
), pp. 367
–378
.10.1111/j.1768-322X.1999.tb01094.x35.
Zhau
, Y.
, and Zhan
, Q.
, 2012
, “Electric Oscillation and Coupling of Chromatics Regulate Chromosome Packaging and Transcription in Eukaryotic Cells
,” Theor. Biol. Med. Modell.
, 9
(1), pp. 27
–38
.10.1186/1742-4682-9-2736.
Hol
, W. G.
, 1985
, “The Role of the Alpha-Helix Dipole in Protein Function and Structure
,” Prog. Biophys. Mol. Biol.
, 45
(3), pp. 149
–155
.10.1016/0079-6107(85)90001-X37.
Sataric
, M. V.
, Tuszynski
, J. A.
, and Pokorny
, J.
, 1993
, “Kinlike Excitations as an Energy-Transfer Mechanism in Microtubules
,” Phys. Rev. E
, 28
, pp. 569
–597
.38.
Brown
, J. A.
, and Tuszynski
, J. A.
, 1999
, “A Review of the Ferroelectric Model of Microtubules
,” Ferroelectrics
, 220
(1), pp. 141
–155
.10.1080/0015019990821621339.
Hameroff
, S. R.
, 2004
, “A New Theory of the Origin of Cancer: Quantum Coherent Entanglement, Centrioles, Mitosis, and Differentiation
,” Bio Systems
, 77
(1–3
), pp. 119
–136
.10.1016/j.biosystems.2004.04.00640.
Pokorny
, J.
, Vedruccio
, C.
, Cifra
, M.
, and Kucera
, O.
, 2011
, “Cancer Physics: Diagnosis Based on Damped Cellular Elastoelectrical Vibrations in Microtubules
,” Eur. Biophys. J.
, 40
(6
), pp. 747
–759
.10.1007/s00249-011-0688-141.
Ridley
, A.
, and Heald
, R.
, 2011
, “Cell Structure and Dynamics—Editorial Overview
,” Curr. Opin. Cell Biol.
, 23
(1
), pp. 1
–3
.10.1016/j.ceb.2010.12.00342.
Asnacious
, A.
, and Hamant
, O.
, 2012
, “The Mechanics Behind Cell Polarity
,” Trends Cell Biol.
, 22
(11
), pp. 584
–591
.10.1016/j.tcb.2012.08.00543.
Salisbury
, J. L.
, Whitehead
, C. M.
, Lingle
, W. L.
, and Barrett
, S. L.
, 1999
, “Centrosomes and Cancer
,” Biol. Cell
, 91
(6
), pp. 451
–460
.10.1111/j.1768-322X.1999.tb01100.x44.
Lingle
, W. L.
, Barrett
, S. L.
, Negron
, V. C.
, D'Assoro
, A. B.
, Boeneman
, K.
, Liu
, W.
, Whitehead
, C. M.
, Reynolds
, C.
, and Salisbury
, J. L.
, 2002
, “Centrosome Amplification Drives Chromosomal Instability in Breast Tumor Development
,” Proc. Natl. Acad. Sci. U.S.A
99
(4
), pp. 1978
–1983
.10.1073/pnas.03247999945.
Raff
, J. W.
, 2002
, “Centrosomes and Cancer: Lessons From a TACC
,” Trends Cell Biol.
, 12
(5
), pp. 222
–225
.10.1016/S0962-8924(02)02268-746.
Pihan
, G. A.
, Wallace
, J.
, Zhou
, Y.
, and Doxsey
, S. J.
, 2003
, “Centrosome Abnormalities and Chromosome Instability Occur Together in Pre-Invasive Carcinomas
,” Cancer Res.
, 63
(6
), pp. 1398
–1404
.47.
Duensing
, A.
, Liu
, Y.
, Perdreau
, S. A.
, Kleylein-Sohn
, J.
, Nigg
, E. Q.
, and Duensing
, S.
, 2007
, “Centriole Overduplication Through the Concurrent Formation of Multiple Daughter Centrioles at Single Material Templates
,” Nature Oncogene
, 26
(43
), pp. 6280
–6288
.10.1038/sj.onc.121045648.
Bettencourt-Dias
, M.
, and Glover
, D. M.
, 2009
, “SnapShot: Centriole Biogenesis
,” Cell
, 136
(1
).10.1016/j.cell.2008.12.03549.
Zyss
, D.
, and Gergely
, F.
, 2009
, “Centrosome Function in Cancer: Guilty or Innocent?
,” Trends Cell Biol.
, 19
(7
), pp. 334
–346
.10.1016/j.tcb.2009.04.00150.
Suresh
, S.
, 2007
, “Biomechanics and Biophysics of Cancer Cells
,” Acta Mater.
55
(12
), pp. 3989
–4014
.10.1016/j.actamat.2007.04.02251.
Binggeli
, R.
, and Weinstein
, R. C.
, 1986
, “Membrane Potentials and Sodium Channels: Hypotheses for Growth Regulation and Cancer Formations Based on Changes in Sodium Channels and Gap Junctions
,” J. Theor. Biol.
, 123
(4), pp. 377
–408
.10.1016/S0022-5193(86)80209-052.
Djarngoz
, M. B. A.
, Mycielska
, M.
, Madeja
, Z.
, Fraser
, S. P.
, and Korohoda
, W.
, 2001
, “Directional Movement of Rat Prostate Cancer Cells in Direct-Current Electric Field: Involvement of Voltage-Gated Na+ Channel Activity
,” J Cell Sci.
, 114
(14), pp. 2597
–2705
.53.
McCaig
, C. D.
, Rajnicek
, A. M.
, Song
, B.
, and Zhao
, M.
, 2005
, “Controlling Cell Behavior Electrically: Current Views and Future Potential
,” Physiol. Rev.
, 86
(3), pp. 943
–978
.10.1152/physrev.00020.200454.
Cuzick
, J.
, Holland
, R.
, Barth
, V.
, Davies
, R.
, Faupel
, M.
, Fentiman
, I.
, Frischbier
, H. J.
, LaMarque
, J. L.
, Merson
, M.
, Sacchini
, V.
, Vanel
, D.
, and Veronesi
, U.
, 1998
, “Electropotential Measurements as a New Diagnostic Modality for Breast Cancer
,” Lancet
, 352
(9125
), pp. 359
–363
.10.1016/S0140-6736(97)10002-255.
Ganem
, N. J.
, Godinho
, S. A.
, and Pellman
, D.
, 2009
, “A Mechanism Linking Extra Centrosomes to Chromosomal Instability
,” Nature
, 460
(7252
), pp. 278
–282
.10.1038/nature0813656.
Vulprecht
, J.
, David
, A.
, Tibelius
, A.
, Castiel
, A.
, Konotop
, G.
, Liu
, F.
, Bestvater
, F.
, Raab
, M. S.
, Zentgraf
, H.
, Izraell
, S.
, and Krämer
, A.
, 2012
, “STIL is Required for Centriole Duplication in Human Cells
,” J. Cell Sci.
, 125
(5
), pp. 1353
–1362
.10.1242/jcs.10410957.
Goepfert
, T. M.
, Adigun
, Y. E.
, Zhong
, L.
, Gay
, J.
, Medina
, D.
, and Brinkley
, W. R.
, 2002
, “Centrosome Amplification and Overexpression of Aurora A are Early Events in Rat Mammary Carcinogenesis
,” Cancer Res.
, 62
(14), pp. 4115
–4122
.58.
Kobayashi
, T.
, and Cynlacht
, B. D.
, 2011
, “Regulating the Transition From Centriole to Basal Body
,” J. Cell Biol.
, 193
(3
), pp. 435
–444
.10.1083/jcb.20110100559.
Lingle
, W. L.
, and Salisbury
, J. L.
, 1999
, “The Role of the Centrosome in the Development of Malignant Tumors
,” Curr. Top. Dev. Biol.
, 49
(1), pp. 313
–339
.10.1016/S0070-2153(99)49015-560.
Schoeckel
, L.
, Moeckel
, M.
, Mayer
, B.
, Boos
, D.
, and Stemmann
, O.
, 2011
, “Cleavage of Cohesion Rings Coordinates the Separation of Centrioles and Chromatides
,” Nat. Cell Biol.
, 13
(8
), pp. 966
–972
.10.1038/ncb228061.
Nigg
, E. A.
, and Raft
, J. W.
, 2009
, “Centrioles, Centrosomes, and Cilia in Health and Disease
,” Cell
, 139
(4
), pp. 663
–678
.10.1016/j.cell.2009.10.03662.
Godinho
, S. A.
, Kwan
, M.
, and Pellman
, D.
, 2009
, “Centrosomes and Cancer: How Cancer Cells Divide With Too Many Centrosomes
,” Cancer Metastasis Rev.
, 28
(1–2
), pp. 85
–98
.10.1007/s10555-008-9163-663.
Brinkley
, B. R.
, 2001
, “Managing the Centrosome Numbers Game: From Chaos to Stability in Cancer Cell Division
,” Trends Cell Biol.
, 11
(1
), pp. 18
–21
.10.1016/S0962-8924(00)01872-964.
D'Assoro
, A. B.
, Lingle
, W. L.
, and Salisbury
, J. L.
, 2002
, “Centrosome Amplification and the Development of Cancer
,” Oncogene
, 21
, pp. 6146
–6153
.10.1038/sj.onc.120577265.
Loffler
, H.
, Fechter
, A.
, Poppelreuther
, S.
, and Kramer
, A.
, 2013
, “DNA Damage-Induced Centrosome Amplification Occurs via Excessive Formation of Centriolar Satellites
,” Oncogene
, 32
, pp. 2963
–2972
.10.1038/onc.2012.31066.
Fukasawa
, K.
, Choi
, T.
, Kuriyama
, P.
, Rulong
, S.
, and VandeWoude
, G. F.
, 1966
, “Abnormal Centrosome Amplication in the Absence of P53
,” Science
, 271
, pp. 1744
–1747
.10.1126/science.271.5256.174467.
Fukasawa
, K.
, 2005
, “Centrosome Amplifications, Chromosome Instability and Cancer Development
,” Cancer Lett.
, 230
, pp. 6
–19
.10.1016/j.canlet.2004.12.02868.
Wong
, C.
, and Stearns
, T.
, 2003
, “Centrosome Number is Controlled by a Centrosome Intrinsic Block to Reduplication
,” Nat. Cell Biol.
, 5
, pp. 539
–544
.10.1038/ncb99369.
Vitre
, B. D.
, and Cleveland
, D. W.
, 2012
, “Centrosomes, Chromosomes Instability (CIN) and Aneuploidy
,” Curr. Opin. Cell Biol.
, 24
, pp. 809
–815
.10.1016/j.ceb.2012.10.00670.
Marthiens
, V.
, Piel
, M.
, and Basto
, R.
, 2012
, “Never Tear us Apart—The Importance of Centrosome Clustering
,” J. Cell Sci.
, 125
, pp. 3281
–3292
.10.1242/jcs.09479771.
McCaig
, C. D.
, Rajnicek
, A. M.
, Song
, B.
, and Zhao
, M.
, 2005
, “Controlling Cell Behavior Electrically: Current Views and Future Potential
,” Physiol. Rev.
, 86
, pp. 943
–978
.10.1152/physrev.00020.200472.
Davies
, R. J.
, Joseph
, R.
, Asbun
, H.
, and Sedwitz
, M.
, 1989
, “Detection of the Cancer-Prone Colon, Using Transepithelial Impedance Analysis
,” Arch. Surg.
, 124
, pp. 480
–484
.10.1001/archsurg.1989.0141004009002173.
Binggeli
, R.
, and Weinstein
, R. C.
, 1986
, “Membrane Potentials and Sodium Channels: Hypotheses for Growth Regulation and Cancer Formations Based on Changes in Sodium Channels and Gap Junctions
,” J. Theor. Biol.
, 123
, pp. 377
–408
.10.1016/S0022-5193(86)80209-074.
Chan
, J. Y.
, 2011
, “A Clinical Overview of Centrosome Amplification in Human Cancers
,” Int. J. Biol. Sci.
, 7
, pp. 1122
–1144
.10.7150/ijbs.7.112275.
Sinder
, G.
, and Nordberg
, J. L.
, 2004
, “The Good, The Bad and The Ugly: The Practical Consequences of Centrosome Amplification
,” Curr. Opin. Cell Biol.
, 16
, pp. 49
–64
.10.1016/j.ceb.2003.11.00676.
Kramer
, A.
, Neben
, K.
, and Ho
, A. D.
, 2002
, “Centrosome Replication, Genomic Instability, and Cancer
,” Leukemia
, 16
, pp. 767
–775
.10.1038/sj.leu.240245477.
Kukasawa
, K.
, 2007
, “Oncogenes and Tumor Suppressors Take on Centrosomes
,” Nat. Rev. Cancer
, 7
, pp. 911
–924
.10.1038/nrc2249Copyright © 2014 by ASME
You do not currently have access to this content.
