Skip to main content
SpringerLink
Log in

Molecular Programs Underlying Asymmetric Stem Cell Division and Their Disruption in Malignancy

  • Chapter
  • First Online:
Asymmetric Cell Division in Development, Differentiation and Cancer

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 61))

Abstract

Asymmetric division of stem cells is a highly conserved and tightly regulated process by which a single stem cell produces two unequal daughter cells. One retains its stem cell identity while the other becomes specialized through a differentiation program and loses stem cell properties. Coordinating these events requires control over numerous intra- and extracellular biological processes and signaling networks. In the initial stages, critical events include the compartmentalization of fate determining proteins within the mother cell and their subsequent passage to the appropriate daughter cell in order to direct their destiny. Disturbance of these events results in an altered dynamic of self-renewing and differentiation within the cell population, which is highly relevant to the growth and progression of cancer. Other critical events include proper asymmetric spindle assembly, extrinsic regulation through micro-environmental cues, and non-canonical signaling networks that impact cell division and fate determination. In this review, we discuss mechanisms that maintain the delicate balance of asymmetric cell division in normal tissues and describe the current understanding how some of these mechanisms are deregulated in cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andreu-Agullo C, Morante-Redolat JM, Delgado AC, Farinas I (2009) Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone. Nat Neurosci 12(12):1514–1523

    Article  CAS  PubMed  Google Scholar 

  • Arama E, Dickman D, Kimchie Z, Shearn A, Lev Z (2000) Mutations in the beta-propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain. Oncogene 19(33):3706–3716

    Article  CAS  PubMed  Google Scholar 

  • Beaucher M, Hersperger E, Page-McCaw A, Shearn A (2007) Metastatic ability of Drosophila tumors depends on MMP activity. Dev Biol 303(2):625–634

    Article  CAS  PubMed  Google Scholar 

  • Besson A, Assoian RK, Roberts JM (2004) Regulation of the cytoskeleton: an oncogenic function for CDK inhibitors? Nat Rev Cancer 4(12):948–955

    Article  CAS  PubMed  Google Scholar 

  • Betschinger J, Mechtler K, Knoblich JA (2003) The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 422(6929):326–330

    Article  CAS  PubMed  Google Scholar 

  • Betschinger J, Eisenhaber F, Knoblich JA (2005) Phosphorylation-induced autoinhibition regulates the cytoskeletal protein Lethal (2) giant larvae. Curr Biol 15(3):276–282

    Article  CAS  PubMed  Google Scholar 

  • Betschinger J, Mechtler K, Knoblich JA (2006) Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 124(6):1241–1253

    Article  CAS  PubMed  Google Scholar 

  • Boulay JL, Stiefel U, Taylor E, Dolder B, Merlo A, Hirth F (2009) Loss of heterozygosity of TRIM3 in malignant gliomas. BMC Cancer 9:71

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bowman SK, Rolland V, Betschinger J, Kinsey KA, Emery G, Knoblich JA (2008) The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell 14(4):535–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bultje RS, Castaneda-Castellanos DR, Jan LY, Jan YN, Kriegstein AR, Shi SH (2009) Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex. Neuron 63(2):189–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caussinus E, Gonzalez C (2005) Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet 37(10):1125–1129

    Article  CAS  PubMed  Google Scholar 

  • Chen G, Kong J, Tucker-Burden C, Anand M, Rong Y, Rahman F, Moreno CS, Van Meir EG, Hadjipanayis CG, Brat DJ (2014) Human Brat ortholog TRIM3 is a tumor suppressor that regulates asymmetric cell division in glioblastoma. Cancer Res 74(16):4536–4548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chenn A, McConnell SK (1995) Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis. Cell 82(4):631–641

    Article  CAS  PubMed  Google Scholar 

  • Chia W, Somers WG, Wang H (2008) Drosophila neuroblast asymmetric divisions: cell cycle regulators, asymmetric protein localization, and tumorigenesis. J Cell Biol 180(2):267–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chieffi P, Cozzolino L, Kisslinger A, Libertini S, Staibano S, Mansueto G, De Rosa G, Villacci A, Vitale M, Linardopoulos S, Portella G, Tramontano D (2006) Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate 66(3):326–333

    Article  CAS  PubMed  Google Scholar 

  • Colaluca IN, Tosoni D, Nuciforo P, Senic-Matuglia F, Galimberti V, Viale G, Pece S, Di Fiore PP (2008) NUMB controls p53 tumour suppressor activity. Nature 451(7174):76–80

    Article  CAS  PubMed  Google Scholar 

  • Conklin EG (1905) The mutation theory from the standpoint of cytology. Science 21(536):525–529

    Article  CAS  PubMed  Google Scholar 

  • Decotto E, Spradling AC (2005) The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals. Dev Cell 9(4):501–510

    Article  CAS  PubMed  Google Scholar 

  • Doetsch F (2003) A niche for adult neural stem cells. Curr Opin Genet Dev 13(5):543–550

    Article  CAS  PubMed  Google Scholar 

  • Du Q, Macara IG (2004) Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119(4):503–516

    Article  CAS  PubMed  Google Scholar 

  • Dudas J, Mansuroglu T, Moriconi F, Haller F, Wilting J, Lorf T, Fuzesi L, Ramadori G (2008) Altered regulation of Prox1-gene-expression in liver tumors. BMC Cancer 8:92

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dyer MA, Livesey FJ, Cepko CL, Oliver G (2003) Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nat Genet 34(1):53–58

    Article  CAS  PubMed  Google Scholar 

  • Eder AM, Sui X, Rosen DG, Nolden LK, Cheng KW, Lahad JP, Kango-Singh M, Lu KH, Warneke CL, Atkinson EN, Bedrosian I, Keyomarsi K, Kuo WL, Gray JW, Yin JC, Liu J, Halder G, Mills GB (2005) Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci USA 102(35):12519–12524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Espinoza I, Pochampally R, Xing F, Watabe K, Miele L (2013) Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition. Onco Targets Ther 6:1249–1259

    PubMed  PubMed Central  Google Scholar 

  • Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269

    Article  CAS  PubMed  Google Scholar 

  • Fukukawa C, Ueda K, Nishidate T, Katagiri T, Nakamura Y (2010) Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells. Genes Chromosomes Cancer 49(10):861–872

    Article  CAS  PubMed  Google Scholar 

  • Fuller MT, Spradling AC (2007) Male and female Drosophila germline stem cells: two versions of immortality. Science 316(5823):402–404

    Article  CAS  PubMed  Google Scholar 

  • Gaiano N, Nye JS, Fishell G (2000) Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26(2):395–404

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Lopez S, Lerner RG, Petritsch C (2013) Asymmetric cell division of stem and progenitor cells during homeostasis and cancer. Cell Mol Life Sci 71(4):575–597

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Habib SJ, Chen BC, Tsai FC, Anastassiadis K, Meyer T, Betzig E, Nusse R (2013) A localized Wnt signal orients asymmetric stem cell division in vitro. Science 339(6126):1445–1448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris RE, Pargett M, Sutcliffe C, Umulis D, Ashe HL (2011) Brat promotes stem cell differentiation via control of a bistable switch that restricts BMP signaling. Dev Cell 20(1):72–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hilliard MA, Bargmann CI (2006) Wnt signals and frizzled activity orient anterior-posterior axon outgrowth in C. elegans. Dev Cell 10(3):379–390

    Article  CAS  PubMed  Google Scholar 

  • Hou C, Ding L, Zhang J, Jin Y, Sun C, Li Z, Sun X, Zhang T, Zhang A, Li H, Gao J (2014) Abnormal cerebellar development and Purkinje cell defects in Lgl1-Pax2 conditional knockout mice. Dev Biol 395(1):167–181

    Article  CAS  PubMed  Google Scholar 

  • Ito T, Kwon HY, Zimdahl B, Congdon KL, Blum J, Lento WE, Zhao C, Lagoo A, Gerrard G, Foroni L, Goldman J, Goh H, Kim SH, Kim DW, Chuah C, Oehler VG, Radich JP, Jordan CT, Reya T (2010) Regulation of myeloid leukaemia by the cell-fate determinant Musashi. Nature 466(7307):765–768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Izumi H, Kaneko Y (2012) Evidence of asymmetric cell division and centrosome inheritance in human neuroblastoma cells. Proc Natl Acad Sci USA 109(44):18048–18053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janic A, Mendizabal L, Llamazares S, Rossell D, Gonzalez C (2010) Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science 330(6012):1824–1827

    Article  CAS  PubMed  Google Scholar 

  • Joberty G, Petersen C, Gao L, Macara IG (2000) The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol 2(8):531–539

    Article  CAS  PubMed  Google Scholar 

  • Kalmes A, Merdes G, Neumann B, Strand D, Mechler BM (1996) A serine-kinase associated with the p127-l(2)gl tumour suppressor of Drosophila may regulate the binding of p127 to nonmuscle myosin II heavy chain and the attachment of p127 to the plasma membrane. J Cell Sci 109(Pt 6):1359–1368

    CAS  PubMed  Google Scholar 

  • Kaltezioti V, Kouroupi G, Oikonomaki M, Mantouvalou E, Stergiopoulos A, Charonis A, Rohrer H, Matsas R, Politis PK (2010) Prox1 regulates the notch1-mediated inhibition of neurogenesis. PLoS Biol 8(12):e1000565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kapinas K, Delany AM (2011) MicroRNA biogenesis and regulation of bone remodeling. Arthritis Res Ther 13(3):220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kapinas K, Grandy R, Ghule P, Medina R, Becker K, Pardee A, Zaidi SK, Lian J, Stein J, van Wijnen A, Stein G (2013) The abbreviated pluripotent cell cycle. J Cell Physiol 228(1):9–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knoblich JA (2008) Mechanisms of asymmetric stem cell division. Cell 132(4):583–597

    Article  CAS  PubMed  Google Scholar 

  • Knoblich JA (2010) Asymmetric cell division: recent developments and their implications for tumour biology. Nat Rev Mol Cell Biol 11(12):849–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Komori H, Xiao Q, McCartney BM, Lee CY (2014) Brain tumor specifies intermediate progenitor cell identity by attenuating beta-catenin/Armadillo activity. Development 141(1):51–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kondo T, Ezzat S, Asa SL (2006) Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 6(4):292–306

    Article  CAS  PubMed  Google Scholar 

  • Konno D, Shioi G, Shitamukai A, Mori A, Kiyonari H, Miyata T, Matsuzaki F (2008) Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat Cell Biol 10(1):93–101

    Article  CAS  PubMed  Google Scholar 

  • Korkut C, Ataman B, Ramachandran P, Ashley J, Barria R, Gherbesi N, Budnik V (2009) Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell 139(2):393–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kunnev D, Ivanov I, Ionov Y (2009) Par-3 partitioning defective 3 homolog (C. elegans) and androgen-induced prostate proliferative shutoff associated protein genes are mutationally inactivated in prostate cancer cells. BMC Cancer 9:318

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kwon C, Cheng P, King IN, Andersen P, Shenje L, Nigam V, Srivastava D (2011) Notch post-translationally regulates beta-catenin protein in stem and progenitor cells. Nat Cell Biol 13(10):1244–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15(3):178–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lathia JD, Hitomi M, Gallagher J, Gadani SP, Adkins J, Vasanji A, Liu L, Eyler CE, Heddleston JM, Wu Q, Minhas S, Soeda A, Hoeppner DJ, Ravin R, McKay RD, McLendon RE, Corbeil D, Chenn A, Hjelmeland AB, Park DM, Rich JN (2011) Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions. Cell Death Dis 2:e200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee CY, Andersen RO, Cabernard C, Manning L, Tran KD, Lanskey MJ, Bashirullah A, Doe CQ (2006a) Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev 20(24):3464–3474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee CY, Robinson KJ, Doe CQ (2006b) Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature 439(7076):594–598

    Article  CAS  PubMed  Google Scholar 

  • Lee CY, Wilkinson BD, Siegrist SE, Wharton RP, Doe CQ (2006c) Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell 10(4):441–449

    Article  CAS  PubMed  Google Scholar 

  • Lehtinen MK, Zappaterra MW, Chen X, Yang YJ, Hill AD, Lun M, Maynard T, Gonzalez D, Kim S, Ye P, D'Ercole AJ, Wong ET, LaMantia AS, Walsh CA (2011) The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron 69(5):893–905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lerner RG, Petritsch C (2014) A microRNA-operated switch of asymmetric-to-symmetric cancer stem cell divisions. Nat Cell Biol 16(3):212–214

    Article  CAS  PubMed  Google Scholar 

  • Li D, Zhu J, Firozi PF, Abbruzzese JL, Evans DB, Cleary K, Friess H, Sen S (2003) Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res 9(3):991–997

    CAS  PubMed  Google Scholar 

  • Li VS, Ng SS, Boersema PJ, Low TY, Karthaus WR, Gerlach JP, Mohammed S, Heck AJ, Maurice MM, Mahmoudi T, Clevers H (2012) Wnt signaling through inhibition of beta-catenin degradation in an intact Axin1 complex. Cell 149(6):1245–1256

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Sato C, Cerletti M, Wagers A (2010) Notch signaling in the regulation of stem cell self-renewal and differentiation. Curr Top Dev Biol 92:367–409

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Raheja R, Yeh N, Ciznadija D, Pedraza AM, Ozawa T, Hukkelhoven E, Erdjument-Bromage H, Tempst P, Gauthier NP, Brennan C, Holland EC, Koff A (2014) TRIM3, a tumor suppressor linked to regulation of p21(Waf1/Cip1.). Oncogene 33(3):308–315

    Article  CAS  PubMed  Google Scholar 

  • Manabe N, Hirai S, Imai F, Nakanishi H, Takai Y, Ohno S (2002) Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells. Dev Dyn 225(1):61–69

    Article  CAS  PubMed  Google Scholar 

  • Mateyak MK, Obaya AJ, Sedivy JM (1999) c-Myc regulates cyclin D-Cdk4 and -Cdk6 activity but affects cell cycle progression at multiple independent points. Mol Cell Biol 19(7):4672–4683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumine A, Ogai A, Senda T, Okumura N, Satoh K, Baeg GH, Kawahara T, Kobayashi S, Okada M, Toyoshima K, Akiyama T (1996) Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein. Science 272(5264):1020–1023

    Article  CAS  PubMed  Google Scholar 

  • Miyata T, Kawaguchi A, Saito K, Kawano M, Muto T, Ogawa M (2004) Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131(13):3133–3145

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee S, Kong J, Brat DJ (2015) Cancer stem cell division: when the rules of asymmetry are broken. Stem Cells Dev 24(4):405–416

    Article  PubMed  Google Scholar 

  • Mukherjee S, Tucker-Burden C, Zhang C, Moberg K, Read R, Hadjipanayis C, Brat DJ (2016) Drosophila Brat and human ortholog TRIM3 maintain stem cell equilibrium and suppress brain tumorigenesis by attenuating Notch nuclear transport. Cancer Res 76(8):2443–2452

    Article  CAS  PubMed  Google Scholar 

  • Nagai H, Li Y, Hatano S, Toshihito O, Yuge M, Ito E, Utsumi M, Saito H, Kinoshita T (2003) Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies. Genes Chromosomes Cancer 38(1):13–21

    Article  CAS  PubMed  Google Scholar 

  • Nesbit CE, Tersak JM, Prochownik EV (1999) MYC oncogenes and human neoplastic disease. Oncogene 18(19):3004–3016

    Article  CAS  PubMed  Google Scholar 

  • Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7(2):136–144

    Article  CAS  PubMed  Google Scholar 

  • Noctor SC, Martinez-Cerdeno V, Kriegstein AR (2008) Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J Comp Neurol 508(1):28–44

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohshiro T, Yagami T, Zhang C, Matsuzaki F (2000) Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature 408(6812):593–596

    Article  CAS  PubMed  Google Scholar 

  • Ota J, Yamashita Y, Okawa K, Kisanuki H, Fujiwara S, Ishikawa M, Lim Choi Y, Ueno S, Ohki R, Koinuma K, Wada T, Compton D, Kadoya T, Mano H (2003) Proteomic analysis of hematopoietic stem cell-like fractions in leukemic disorders. Oncogene 22(36):5720–5728

    Article  CAS  PubMed  Google Scholar 

  • Page SL, McKim KS, Deneen B, Van Hook TL, Hawley RS (2000) Genetic studies of mei-P26 reveal a link between the processes that control germ cell proliferation in both sexes and those that control meiotic exchange in Drosophila. Genetics 155(4):1757–1772

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pan L, Chen S, Weng C, Call G, Zhu D, Tang H, Zhang N, Xie T (2007) Stem cell aging is controlled both intrinsically and extrinsically in the Drosophila ovary. Cell Stem Cell 1(4):458–469

    Article  CAS  PubMed  Google Scholar 

  • Peng CY, Manning L, Albertson R, Doe CQ (2000) The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Nature 408(6812):596–600

    Article  CAS  PubMed  Google Scholar 

  • Perez-Losada J, Balmain A (2003) Stem-cell hierarchy in skin cancer. Nat Rev Cancer 3(6):434–443

    Article  CAS  PubMed  Google Scholar 

  • Quinn LM, Secombe J, Hime GR (2013) Myc in stem cell behaviour: insights from Drosophila. Adv Exp Med Biol 786:269–285

    Article  CAS  PubMed  Google Scholar 

  • Rhiner C, Diaz B, Portela M, Poyatos JF, Fernandez-Ruiz I, Lopez-Gay JM, Gerlitz O, Moreno E (2009) Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche. Development 136(6):995–1006

    Article  CAS  PubMed  Google Scholar 

  • Roeder I, Lorenz R (2006) Asymmetry of stem cell fate and the potential impact of the niche: observations, simulations, and interpretations. Stem Cell Rev 2(3):171–180

    Article  PubMed  Google Scholar 

  • Rothenberg SM, Mohapatra G, Rivera MN, Winokur D, Greninger P, Nitta M, Sadow PM, Sooriyakumar G, Brannigan BW, Ulman MJ, Perera RM, Wang R, Tam A, Ma XJ, Erlander M, Sgroi DC, Rocco JW, Lingen MW, Cohen EE, Louis DN, Settleman J, Haber DA (2010) A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers. Cancer Res 70(6):2158–2164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwamborn JC, Berezikov E, Knoblich JA (2009) The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 136(5):913–925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, Abramova N, Vincent P, Pumiglia K, Temple S (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304(5675):1338–1340

    Article  CAS  PubMed  Google Scholar 

  • Shitamukai A, Konno D, Matsuzaki F (2011) Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors. J Neurosci 31(10):3683–3695

    Article  CAS  PubMed  Google Scholar 

  • Siegrist SE, Doe CQ (2005) Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell 123(7):1323–1335

    Article  CAS  PubMed  Google Scholar 

  • Siller KH, Cabernard C, Doe CQ (2006) The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nat Cell Biol 8(6):594–600

    Article  CAS  PubMed  Google Scholar 

  • Slack C, Overton PM, Tuxworth RI, Chia W (2007) Asymmetric localisation of Miranda and its cargo proteins during neuroblast division requires the anaphase-promoting complex/cyclosome. Development 134(21):3781–3787

    Article  CAS  PubMed  Google Scholar 

  • Song X, Zhu CH, Doan C, Xie T (2002) Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science 296(5574):1855–1857

    Article  CAS  PubMed  Google Scholar 

  • Sonoda J, Wharton RP (2001) Drosophila Brain Tumor is a translational repressor. Genes Dev 15(6):762–773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi M, Yoshimoto T, Shimoda M, Kono T, Koizumi M, Yazumi S, Shimada Y, Doi R, Chiba T, Kubo H (2006) Loss of function of the candidate tumor suppressor prox1 by RNA mutation in human cancer cells. Neoplasia 8(12):1003–1010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Troy A, Cadwallader AB, Fedorov Y, Tyner K, Tanaka KK, Olwin BB (2012) Coordination of satellite cell activation and self-renewal by Par-complex-dependent asymmetric activation of p38alpha/beta MAPK. Cell Stem Cell 11(4):541–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verbist KC, Guy CS, Milasta S, Liedmann S, Kaminski MM, Wang R, Green DR (2016) Metabolic maintenance of cell asymmetry following division in activated T lymphocytes. Nature 532(7599):389–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Versmold B, Felsberg J, Mikeska T, Ehrentraut D, Kohler J, Hampl JA, Rohn G, Niederacher D, Betz B, Hellmich M, Pietsch T, Schmutzler RK, Waha A (2007) Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer. Int J Cancer 121(3):547–554

    Article  CAS  PubMed  Google Scholar 

  • Vessey JP, Amadei G, Burns SE, Kiebler MA, Kaplan DR, Miller FD (2012) An asymmetrically localized Staufen2-dependent RNA complex regulates maintenance of mammalian neural stem cells. Cell Stem Cell 11(4):517–528

    Article  CAS  PubMed  Google Scholar 

  • Viloria-Petit AM, David L, Jia JY, Erdemir T, Bane AL, Pinnaduwage D, Roncari L, Narimatsu M, Bose R, Moffat J, Wong JW, Kerbel RS, O'Malley FP, Andrulis IL, Wrana JL (2009) A role for the TGFbeta-Par6 polarity pathway in breast cancer progression. Proc Natl Acad Sci USA 106(33):14028–14033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Somers GW, Bashirullah A, Heberlein U, Yu F, Chia W (2006) Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes Dev 20(24):3453–3463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wirtz-Peitz F, Nishimura T, Knoblich JA (2008) Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell 135(1):161–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wodarz A, Nathke I (2007) Cell polarity in development and cancer. Nat Cell Biol 9(9):1016–1024

    Article  CAS  PubMed  Google Scholar 

  • Wodarz A, Ramrath A, Kuchinke U, Knust E (1999) Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts. Nature 402(6761):544–547

    Article  CAS  PubMed  Google Scholar 

  • Woods DF, Hough C, Peel D, Callaini G, Bryant PJ (1996) Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia. J Cell Biol 134(6):1469–1482

    Article  CAS  PubMed  Google Scholar 

  • Yamanaka T, Horikoshi Y, Sugiyama Y, Ishiyama C, Suzuki A, Hirose T, Iwamatsu A, Shinohara A, Ohno S (2003) Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Curr Biol 13(9):734–743

    Article  CAS  PubMed  Google Scholar 

  • Yamashita YM, Mahowald AP, Perlin JR, Fuller MT (2007) Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science 315(5811):518–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yong KJ, Yan B (2011) The relevance of symmetric and asymmetric cell divisions to human central nervous system diseases. J Clin Neurosci 18(4):458–463

    Article  PubMed  Google Scholar 

  • Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen AJ, Perry SR, Tonon G, Chu GC, Ding Z, Stommel JM, Dunn KL, Wiedemeyer R, You MJ, Brennan C, Wang YA, Ligon KL, Wong WH, Chin L, dePinho RA (2008) Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma. Cold Spring Harb Symp Quant Biol 73:427–437

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA

    Subhas Mukherjee & Daniel J. Brat M.D., Ph.D.

  2. Winship Cancer Institute, Emory University, 1701 Uppergate Drive, Building C, Rm#C5038, Atlanta, GA, USA

    Daniel J. Brat M.D., Ph.D.

Authors
  1. Subhas Mukherjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel J. Brat M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel J. Brat M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. IGDR, UMR 6290, CNRS, Université de Rennes 1, Rennes, France

    Jean-Pierre Tassan

  2. Inst of Genetics & Dev of Rennes IG, CNRS/Unive Rennes 1 UMR 6290, Rennes Cedex, France

    Jacek Z. Kubiak

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Mukherjee, S., Brat, D.J. (2017). Molecular Programs Underlying Asymmetric Stem Cell Division and Their Disruption in Malignancy. In: Tassan, JP., Kubiak, J. (eds) Asymmetric Cell Division in Development, Differentiation and Cancer. Results and Problems in Cell Differentiation, vol 61. Springer, Cham. https://doi.org/10.1007/978-3-319-53150-2_18

Download citation

Publish with us

Policies and ethics

Search

Navigation