An Introduction to Proliferation and Migration of Stem and Cancer Cells

  • Micheli Mainardi Pillat
  • Talita Glaser
  • Telma Tiemi Schwindt
  • Henning UlrichEmail author


Throughout life, complex genetic systems regulate the balance between cell birth and death in response to growth and death signals. During early development, only a few cells abandon the cycle, but in several adult tissues, the cells normally do not proliferate, except during healing processes, which are supported by stem cells. However, in some adult tissues, cells continuously divide as a strategy for constant tissue renewal. In this context, cancer occurs when the control of growth and death is defective, driving the cells to an erroneous escape from death and causing intense cell proliferation. In the same way, the mechanisms and processes that coordinate cell migration are related to cell–cell contact and are important for homeostasis and the constitution of the organism. Moreover, migration is a normal event during embryo development and tissue regeneration; however, when regulation of migration fails, this can lead to a diverse number of diseases, including cancer. This chapter introduces the reader to the following specialized chapters on proliferation mechanisms written by experts in the field.


Stem cells Cell proliferation Cancer Migration 


  1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988PubMedCrossRefGoogle Scholar
  2. Ayalon O, Geiger B (1997) Cyclic changes in the organization of cell adhesions and the associated cytoskeleton, induced by stimulation of tyrosine phosphorylation in bovine aortic endothelial cells. J Cell Sci 110:547–556PubMedGoogle Scholar
  3. Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A (2000) The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2:84–89PubMedCrossRefGoogle Scholar
  4. Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A (2003) The transcription factor slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with snail and E47 repressors. J Cell Sci 116:499–511PubMedCrossRefGoogle Scholar
  5. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737PubMedCrossRefGoogle Scholar
  6. Carver EA, Jiang R, Lan Y, Oram KF, Gridley T (2001) The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol 21:8184–8188PubMedCrossRefGoogle Scholar
  7. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951PubMedCrossRefGoogle Scholar
  8. Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D, van Roy F (2001) The two-handed E box binding zinc finger protein SIP1 downregulates e-cadherin and induces invasion. Mol Cell 7:1267–1278PubMedCrossRefGoogle Scholar
  9. Conrad PA, Giuliano KA, Fisher G, Collins K, Matsudaira PT, Taylor DL (1993) Relative distribution of actin, myosin I, and myosin II during the wound healing response of fibroblasts. J Cell Biol 120:1381–1391PubMedCrossRefGoogle Scholar
  10. Cui H, Hu B, Li T, Ma J, Alam G, Gunning WT, Ding HF (2007) Bmi-1 is essential for the tumorigenicity of neuroblastoma cells. Am J Pathol 170:1370–1378PubMedCrossRefGoogle Scholar
  11. Deckbar D, Jeggo PA, Lobrich M (2011) Understanding the limitations of radiation-induced cell cycle checkpoints. Crit Rev Biochem Mol Biol 46:271–283PubMedCrossRefGoogle Scholar
  12. Dick JE (2008) Stem cell concepts renew cancer research. Blood 112:4793–4807PubMedCrossRefGoogle Scholar
  13. Dixon R, Rosendaal M (1981) Contrasts between the response of the mouse haemopoietic system to 5-fluorouracil and irradiation. Blood cells 7:575–587PubMedGoogle Scholar
  14. Grinstein E, Wernet P (2007) Cellular signaling in normal and cancerous stem cells. Cell Signal 19:2428–2433PubMedCrossRefGoogle Scholar
  15. Grooteclaes ML, Frisch SM (2000) Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene 19:3823–3828PubMedCrossRefGoogle Scholar
  16. Hartwell LH, Weinert TA (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 246:629–634PubMedCrossRefGoogle Scholar
  17. Haupt Y, Alexander WS, Barri G, Klinken SP, Adams JM (1991) Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell 65:753–763PubMedCrossRefGoogle Scholar
  18. Janmey PA (1994) Phosphoinositides and calcium as regulators of cellular actin assembly and disassembly. Annu Rev Physiol 56:169–191PubMedCrossRefGoogle Scholar
  19. Khew-Goodall Y, Wadham C (2005) A perspective on regulation of cell–cell adhesion and epithelial-mesenchymal transition: known and novel. Cells Tissues Organs 179:81–86PubMedCrossRefGoogle Scholar
  20. Lauffenburger DA, Horwitz AF (1996) Cell migration: a physically integrated molecular process. Cell 84:359–369PubMedCrossRefGoogle Scholar
  21. Lessard J, Sauvageau G (2003) Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423:255–260PubMedCrossRefGoogle Scholar
  22. Leung C, Lingbeek M, Shakhova O, Liu J, Tanger E, Saremaslani P, Van Lohuizen M, Marino S (2004) Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428:337–341PubMedCrossRefGoogle Scholar
  23. Li L, Bhatia R (2011) Stem cell quiescence. Clin Cancer Res 17:4936–4941PubMedCrossRefGoogle Scholar
  24. Malumbres M, Barbacid M (2001) To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 1:222–231PubMedCrossRefGoogle Scholar
  25. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9:153–166PubMedCrossRefGoogle Scholar
  26. Maxfield FR (1993) Regulation of leukocyte locomotion by Ca2+. Trends Cell Biol 3:386–391PubMedCrossRefGoogle Scholar
  27. Moore N, Lyle S (2011) Quiescent, slow-cycling stem cell populations in cancer: a review of the evidence and discussion of significance. J Oncol 2011:396076Google Scholar
  28. Morgan DO (1997) Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu Rev Cell Dev Biol 13:261–291PubMedCrossRefGoogle Scholar
  29. Ozawa M, Kemler R (1998a) Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex. J Biol Chem 273:6166–6170PubMedCrossRefGoogle Scholar
  30. Ozawa M, Kemler R (1998b) The membrane-proximal region of the E-cadherin cytoplasmic domain prevents dimerization and negatively regulates adhesion activity. J Cell Biol 142:1605–1613PubMedCrossRefGoogle Scholar
  31. Prindull G, Zipori D (2004) Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm. Blood 103:2892–2899PubMedCrossRefGoogle Scholar
  32. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111PubMedCrossRefGoogle Scholar
  33. Roura S, Miravet S, Piedra J, Garcia de Herreros A, Dunach M (1999) Regulation of E-cadherin/Catenin association by tyrosine phosphorylation. J Biol Chem 274:36734–36740PubMedCrossRefGoogle Scholar
  34. Sang L, Coller HA, Roberts JM (2008) Control of the reversibility of cellular quiescence by the transcriptional repressor HES1. Science 321:1095–1100PubMedCrossRefGoogle Scholar
  35. Sheetz MP (1994) Cell migration by graded attachment to substrates and contraction. Semin Cell Biol 5:149–155PubMedCrossRefGoogle Scholar
  36. Shinagawa K, Kitadai Y, Tanaka M, Sumida T, Kodama M, Higashi Y, Tanaka S, Yasui W, Chayama K (2010) Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer 127:2323–2333PubMedCrossRefGoogle Scholar
  37. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828PubMedGoogle Scholar
  38. Siu MK, Wong ES, Kong DS, Chan HY, Jiang L, Wong OG, Lam EW, Chan KK, Ngan HY, Le XF, Cheung AN (2012) Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers. OncogeneGoogle Scholar
  39. Sullivan SJ, Daukas G, Zigmond SH (1984) Asymmetric distribution of the chemotactic peptide receptor on polymorphonuclear leukocytes. J Cell Biol 99:1461–1467PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Micheli Mainardi Pillat
    • 1
  • Talita Glaser
    • 1
  • Telma Tiemi Schwindt
    • 2
  • Henning Ulrich
    • 1
    Email author
  1. 1.Departamento de Bioquímica, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil
  2. 2.Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências BiomédicasUniversidade de São PauloSão PauloBrazil

Personalised recommendations