Overview of cancer stem cells (CSCS) and mechanisms of their regulation: Implications for cancer therapy

Current Protocols in Pharmacology

Volumn , Issue SUPPL.61, 2013, Pages

  Bao, Bin ^a   Ahmad, Aamir ^a   Azmi, Asfar S ^a   Ali, Shadan ^a   Sarkar, Fazlul H ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cell surface markers; CSCs; Metformin; MiRNAs

Indexed keywords

METFORMIN; MICRORNA; MICRORNA 200; MICRORNA 21; MICRORNA 34A; TUMOR MARKER; ANTIDIABETIC AGENT;

ACUTE GRANULOCYTIC LEUKEMIA; ARTICLE; BREAST CANCER; CANCER PREVENTION; CANCER RESISTANCE; CANCER STEM CELL; CANCER THERAPY; CANCER TISSUE; CELL DESTRUCTION; CELL DIFFERENTIATION; CELL ISOLATION; CELL MIGRATION; CELL RENEWAL; CELL SUBPOPULATION; DRUG TARGETING; HUMAN; LUNG CANCER; METASTASIS; MONONUCLEAR CELL; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; TREATMENT OUTCOME; TUMOR INVASION; ANIMAL MODEL; METABOLISM; NEOPLASM; PATHOLOGY; PHYSIOLOGY; REVIEW; NEOPLASMS;

HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; MICRORNAS; MODELS, ANIMAL; NEOPLASMS; NEOPLASTIC STEM CELLS; TUMOR MARKERS, BIOLOGICAL;

EID: 84883165709     PISSN: 19348282     EISSN: 19348290     Source Type: Journal    
DOI: 10.1002/0471141755.ph1425s61     Document Type: Article

References (113)

1. Akunuru, S., Palumbo, J., Zhai, Q.J.,and Zheng,Y.2011. Rac1 targeting suppresses human nonsmall cell lung adenocarcinoma cancer stem cell activity. PLoS One 6:e16951.
2. Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., and Clarke, M.F. 2003. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 100:3983-3988.
3. Ali, S., Ahmad, A., Banerjee, S., Padhye, S., Dominiak, K., Schaffert, J.M.,Wang, Z., Philip, P.A., and Sarkar, F.H. 2010. Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. Cancer Res. 70:3606-3617.
4. Aranha, M.M., Santos, D.M., Soĺa, S., Steer, C.J., and Rodrigues, C.M.P. 2011. miR-34a regulates mouse neural stem cell differentiation.PLoS One6:e21396.
5. Bao, B., Wang, Z., Ali, S., Kong, D., Li, Y., Ahmad, A., Banerjee, S., Azmi, A.S., Miele, L., and Sarkar, F.H. 2011. Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells. Cancer Lett. 307:26-36.
6. Bao, B., Ahmad, A., Li, Y., Azmi, A.S., Ali, S., Banerjee, S., Kong, D., and Sarkar, F.H. 2012a. Targeting CSCs within the tumor microenvironment for cancer therapy:Apotential role ofmesenchymal stem cells. Exp. Opin. Ther. Targets 16:1041-1054.
7. Bao, B., Ali, S., Banerjee, S., Wang, Z., Logna, F., Azmi, A.S., Kong, D., Ahmad, A., Li, Y., Padhye, S., and Sarkar, F.H. 2012b. Curcuminanalogue CDF inhibits pancreatic tumor growthby switching on suppressor microRNAs and attenuating EZH2 expression. Cancer Res. 72:335-345.
8. Bao, B., Wang, Z., Ali, S., Ahmad, A., Azmi, A.S., Sarkar, S.H., Banerjee, S., Kong, D., Li, Y., Thakur, S., and Sarkar, F.H. 2012c. Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulatingmiRNAs in pancreatic cancer cells. Cancer Prev. Res. 5:355-364.
9. Bao, S., Wu, Q., McLendon, R.E., Hao, Y., Shi, Q., Hjelmeland, A.B., Dewhirst, M.W., Bigner, D.D., and Rich, J.N. 2006. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756-760.
10. Bauerschmitz, G.J., Ranki, T., Kangasniemi, L., Ribacka, C., Eriksson, M., Porten, M., Herrmann, I., Ristimaki, A., Virkkunen, P., Tarkkanen, M., Hakkarainen, T., Kanerva, A., Rein, D., Pesonen, S., and Hemminki, A. 2008. Tissuespecific promoters active in CD44+CD24-/low breast cancer cells. Cancer Res. 68:5533-5539.
11. Ben Sahra, I., Le Marchand-Brustel, Y., Tanti, J.-F., and Bost, F. 2010. Metformin in cancer therapy: A new perspective for an old antidiabetic drug? Mol. Cancer Ther. 9:1092-1099.
12. Bennett, J.M., Catovsky, D., Daniel, M.-T., Flandrin, G., Galton, D.A.G., Gralnick, H.R., and Sultan, C. 1985. Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7): A report of the French-American-British Cooperative Group. Ann. Intern. Med. 103:460-462.
13. Bhatia, M., Wang, J.C.Y., Kapp, U., Bonnet, D., and Dick, J.E. 1997. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 94:5320-5325.
14. Blair, A. and Sutherland, H.J. 2000. Primitive acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo lack surface expression of c-kit (CD117). Exp. Hematol. 28:660-671.
15. Blair, A.,Hogge,D.E., Ailles, L.E., Lansdorp, P.M., and Sutherland, H.J. 1997. Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood 89:3104-3112.
16. Bonnet, D. and Dick, J.E. 1997. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3:730-737.
17. Bowker, S.L., Majumdar, S.R., Veugelers, P., and Johnson, J.A. 2006. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 29:254-258.
18. Budel, L.M., Touw, I.P., Delwel, R., Clark, S.C., and Lowenberg, B. 1989. Interleukin-3 and granulocyte-monocyte colony-stimulating factor receptors on human acute myelocytic leukemia cells and relationship to the proliferative response. Blood 74:565-571.
19. Cazzaniga, M., Bonanni, B., Guerrieri-Gonzaga, A., and Decensi, A. 2009. Is it time to test metformin in breast cancer clinical trials? Cancer Epidemiol. Biomarkers Prev. 18:701-705.
20. Chang, C.-J., Hsu, C.-C., Chang, C.-H., Tsai, L.-L., Chang, Y.-C., Lu, S.-W., Yu, C.-H., Huang, H.-S.,Wang, J.-J., Tsai, C.-H., Chou, M.-Y., Yu, C.-C., and Hu, F.-W. 2011. Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer. Oncol. Rep. 26:1003-1010.
21. Charafe-Jauffret, E., Ginestier, C., Iovino, F., Wicinski, J., Cervera, N., Finetti, P., Hur, M.-H., Diebel, M.E., Monville, F., Dutcher, J., Brown, M., Viens, P., Xerri, L., Bertucci, F., Stassi, G., Dontu, G.,Birnbaum, D., andWicha, M.S. 2009. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 69:1302-1313.
22. Creighton, C.J., Chang, J.C., and Rosen, J.M. 2010. Epithelial-mesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer. J. Mammary Gland Biol. Neoplasia 15:253-260.
23. Croker, A.K., Goodale, D., Chu, J., Postenka, C., Hedley, B.D., Hess, D.A., and Allan, A.L. 2009. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J. Cell Mol. Med. 13:2236-2252.
24. Dick, J.E. 2005. Acute myeloid leukemia stem cells. Ann. N.Y. Acad. Sci. 1044:1-5. Dillhoff, M., Liu, J., Frankel, W., Croce, C., and Bloomston, M. 2008. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J. Gastrointest. Surg.12:2171-2176.
25. Dowling, R.J.O., Zakikhani, M., Fantus, I.G., Pollak, M., and Sonenberg, N. 2007. Metformin inhibits mammalian target of rapamycindependent translation initiation in breast cancer cells. Cancer Res. 67:10804-10812.
26. Dylla, S.J., Beviglia, L., Park, I.-K., Chartier, C., Raval, J., Ngan, L., Pickell, K., Aguilar, J., Lazetic, S., Smith-Berdan, S., Clarke, M.F., Hoey, T., Lewicki, J., and Gurney, A.L. 2008. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One 3:e2428.
27. Edwards, B.K., Brown, M.L., Wingo, P.A., Howe, H.L., Ward, E., Ries, L.A.G., Schrag, D., Jamison, P.M., Jemal, A., Wu, X.C., Friedman, C., Harlan, L., Warren, J., Anderson, R.N., and Pickle, L.W. 2005. Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment. J. Natl. Cancer Inst. 97:1407-1427.
28. Engelmann, K., Shen, H., and Finn, O.J. 2008. MCF7 side population cells with characteristics of cancer stem/progenitor cells express thetumor antigen MUC1. Cancer Res. 68:2419-2426.
29. Eramo, A., Haas, T.L.,and De Maria, M.2010. Lung cancer stem cells: Tools and targets to fight lung cancer. Oncogene 29:4625-4635.
30. Ersoy, C., Kiyici, S., Budak, F., Oral, B., Guclu, M., Duran, C., Selimoglu, H., Erturk, E., Tuncel, E., and Imamoglu, S. 2008. The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients. Diabetes Res. Clin. Pract. 81:56-60.
31. Fabbri, M., Ivan, M.,Cimmino, A.,Negrini,M., and Calin, G.A. 2007. Regulatory mechanisms of microRNAs involvement in cancer. Exp. Opin. Biol. Ther. 7:1009-1019.
32. Feng, Z., Hu,W., de Stanchina, E., Teresky, A.K., Jin, S., Lowe, S., and Levine, A.J. 2007. The regulation of AMPK beta1, TSC2, and PTEN expression by p53: Stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res. 67:3043-3053.
33. Fields, A.P. and Regala, R.P. 2007. Protein kinase C iota: Human oncogene, prognostic marker and therapeutic target. Pharmacol. Res. 55:487-497.
34. Ginestier, C., Hur, M.H., Charafe-Jauffret, E., Monville, F., Dutcher, J., Brown, M., Jacquemier, J., Viens, P., Kleer, C.G., Liu, S., Schott, A., Hayes, D., Birnbaum, D., Wicha, M.S., and Dontu, G. 2007. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555-567.
35. Golestaneh, A.F., Atashi, A., Langroudi, L., Shafiee, A., Ghaemi, N., and Soleimani, M. 2012. miRNAs expressed differently in cancer stem cells and cancer cells of human gastric cancer cell line MKN-45. Cell. Biochem. Funct. 30:411-418.
36. Goodwin, P.J., Ligibel, J.A., and Stambolic, V. 2009. Metformin in breast cancer: Time for action. J. Clin. Oncol. 27:3271-3273.
37. Guo, Y., Li, S., Qu, J., Wang, S., Dang, Y., Fan, J., Yu, S., and Zhang, J. 2011. MiR-34a inhibits lymphatic metastasis potential of mouse hepatoma cells. Mol. Cell. Biochem. 354:275-282.
38. Han, M., Wang, Y., Liu, M., Bi, X., Bao, J., Zeng, N., Zhu, Z.,Mo, Z.,Wu, C., and Chen, X. 2012. MiR-21 regulates epithelial-mesenchymal transition phenotype and hypoxia-inducible factor-1α expression in third-sphere forming breast cancer stem cell-like cells. Cancer Sci. 103:1058-1064.
39. Heikkinen, S., Auwerx, J., and Argmann, C.A. 2007. PPARγ in human and mouse physiology. Biochim. Biophys. Acta 1771:999-1013.
40. Hermann, P.C., Huber, S.L., Herrler, T., Aicher, A., Ellwart, J.W., Guba, M., Bruns, C.J., and Heeschen, C. 2007. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313-323.
41. Hikita, S.T., Kosik, K.S., Clegg, D.O., and Bamdad, C. 2008. MUC1* mediates the growth of human pluripotent stem cells. PLoS One 3:e3312.
42. Hirsch, H.A., Iliopoulos, D., Tsichlis, P.N., and Struhl, K. 2009. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 69:7507-7511.
43. Ho, M.M., Ng, A.V., Lam, S., and Hung, J.Y. 2007. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 67:4827-4833.
44. Hong, S.P., Wen, J., Bang, S., Park, S., and Song, S.Y. 2009. CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. Int. J. Cancer 125:2323-2331.
45. Huang, N.L., Chiang, S.H., Hsueh, C.H., Liang, Y.J., Chen, Y.J., and Lai, L.P. 2009. Metformin inhibits TNF-α-induced IκB kinase phosphorylation, IκB-α degradation and IL-6 production in endothelial cells through PI3Kdependent AMPK phosphorylation. Int. J. Cardiol. 134:169-175.
46. Hurt, E.M., Kawasaki, B.T., Klarmann, G.J., Thomas, S.B., and Farrar, W.L. 2008. CD44+ CD24- prostate cells are early cancer progenitor/ stem cells that provide a model for patients with poor prognosis. Br. J. Cancer 98:756-765.
47. Iliopoulos, D., Lindahl-Allen, M., Polytarchou, C., Hirsch,H.A., Tsichlis, P.N., and Struhl,K. 2010. Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol. Cell 39:761-772.
48. Jin, L., Hope, K.J., Zhai, Q., Smadja-Joffe, F., and Dick, J.E. 2006. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat. Med. 12:1167-1174.
49. Jin, L., Lee, E.M., Ramshaw, H.S., Busfield, S.J., Peoppl, A.G., Wilkinson, L., Guthridge, M.A., Thomas, D., Barry, E.F., Boyd, A., Gearing, D.P., Vairo, G., Lopez, A.F., Dick, J.E., and Lock, R.B. 2009. Monoclonal antibodymediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell 5:31-42.
50. Johnsen, H.E., Kjeldsen, M.K., Urup, T., Fogd, K., Pilgaard, L.,Boegsted, M.,Nyegaard, M.,Christiansen, I., Bukh, A., and Dybkaer, K. 2009. Cancer stem cells and the cellular hierarchy in haematological malignancies. Eur. J. Cancer 45:S194-S201.
51. Jordan, C.T., Upchurch, D., Szilvassy, S.J., Guzman, M.L., Howard, D.S., Pettigrew, A.L., Meyerrose, T., Rossi, R., Grimes, B., Rizzieri, D.A., Luger, S.M., and Phillips, G.L. 2000. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 14:1777-1784.
52. Kasper, S. 2009. Identification, characterization, and biological relevance of prostate cancer stem cells from clinical specimens. Urol. Oncol. 27:301-303. Kent, O.A., Mullendore, M.E., Wentzel, E.A., Ĺopez-Romero, P., Tan, A.C.,Alvarez, H.,West, K., Ochs, M.F., Hidalgo, M., Arking, D.E., Maitra, A., and Mendell, J.T. 2009. A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells. Cancer Biol. Ther. 8:2013-2024.
53. Kisfalvi, K., Eibl, G., Sinnett-Smith, J., and Rozengurt, E. 2009. Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Res. 69:6539-6545.
54. Kissil, J.L., Walmsley, M.J., Hanlon, L., Haigis, K.M., Bender Kim, C.F., Sweet-Cordero, A., Eckman, M.S., Tuveson, D.A., Capobianco, A.J., Tybulewicz, V.L.J., and Jacks, T. 2007. Requirement for Rac1 in a K-ras induced lung cancer in the mouse. Cancer Res. 67:8089-8094.
55. Kitamura, H., Okudela, K., Yazawa, T., Sato, H., and Shimoyamada, H. 2009. Cancer stem cell: Implications in cancer biology and therapy with special reference to lung cancer. Lung Cancer 66:275-281.
56. Klein, R.S., Rubin, J.B., Gibson, H.D., DeHaan, E.N., Alvarez-Hernandez, X., Segal, R.A., and Luster, A.D. 2001. SDF-1α induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development 128:1971-1981.
57. Klonisch, T., Wiechec, E., Hombach-Klonisch, S., Ande, S.R., Wesselborg, S., Schulze-Osthoff, K., and Los, M. 2008. Cancer stem cell markers in common cancers-therapeutic implications. Trends Mol. Med. 14:450-460.
58. Kong, D., Li, Y., Wang, Z., Banerjee, S., Ahmad, A., Kim, H.R.-C., and Sarkar, F.H. 2009. miR-200 regulates PDGF-D-mediated epithelialmesenchymal transition, adhesion, and invasion of prostate cancer cells. Stem Cells 27:1712-1721.
59. Kong, D., Banerjee, S., Ahmad, A., Li, Y., Wang, Z., Sethi, S., and Sarkar, F.H. 2010. Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS One 5:e12445.
60. Kong, D., Heath, E., Chen,W., Cher, M.L., Powell, I., Heilbrun, L., Li, Y., Ali, S., Sethi, S., Hassan, O., Hwang, C., Gupta, N., Chitale, D., Sakr, W.A., Menon, M., and Sarkar, F.H. 2012a. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One 7:e33729.
61. Kong, D., Heath, E., Chen,W., Cher, M., Powell, I., Heilbrun, L., Li,Y.,Ali, S., Sethi, S., Hassan, O., Hwang, C., Gupta, N., Chitale, D., Sakr, W.A., Menon, M., and Sarkar, F.H. 2012b. Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment. Am. J. Transl. Res. 4:14-23.
62. Kufe, D.W. 2013. MUC1-C oncoprotein as a target in breast cancer: Activation of signaling pathways and therapeutic approaches. Oncogene 32:1073-1081.
63. Landman, G.W.D., Kleefstra, N., van Hateren, K.J.J., Groenier, K.H., Gans, R.O.B., and Bilo, H.J.G. 2010. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care 33:322-326.
64. Leal, J.A. and Lleonart, M.E. 2012. MicroRNAs and cancer stem cells: Therapeutic approaches and future perspectives. Cancer Lett. In press.
65. Lee, C.J., Dosch, J., and Simeone, D.M. 2008. Pancreatic cancer stem cells. J. Clin. Oncol. 26:2806-2812.
66. Li,C., Heidt,D.G., Dalerba, P., Burant,C.F., Zhang, L., Adsay, V., Wicha, M., Clarke, M.F., and Simeone, D.M. 2007. Identification of pancreatic cancer stem cells. Cancer Res. 67:1030-1037.
67. Li, Y., VandenBoom, T.G., Kong, D., Wang, Z., Ali, S., Philip, P.A., and Sarkar, F.H. 2009. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelialto-mesenchymal transition in gemcitabineresistant pancreatic cancer cells. Cancer Res. 69:6704-6712.
68. Li, Y., Kong, D., Ahmad, A., Bao, B., and Sarkar, F.H. 2012. Pancreatic cancer stem cells: Emerging target for designing novel therapy. Cancer Lett. In press.
69. Libby, G., Donnelly, L.A., Donnan, P.T., Alessi, D.R., Morris, A.D., and Evans, J.M.M. 2009. New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes. Diabetes Care 32:1620-1625.
70. Liu, C. and Tang, D.G. 2011. MicroRNA regulation of cancer stem cells. Cancer Res. 71:5950-5954.
71. Lodygin, D., Tarasov, V., Epanchintsev, A., Berking, C., Knyazeva, T., K̈orner, H., Knyazev, P., Diebold, J., and Hermeking, H. 2008. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle 7:2591-2600.
72. Lund, S.S., Tarnow, L., Stehouwer, C.D.A., Schalkwijk, C.G., Teerlink, T., Gram, J., Winther, K., Frandsen, M., Smidt, U.M., Pedersen, O., Parving, H.-H., and Vaag, A.A. 2008. Impact of metformin versus repaglinide on non-glycaemic cardiovascular riskmarkers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. Eur. J. Endocrinol. 158:631-641.
73. Majeti, R.,Chao, M.P.,Alizadeh,A.A., Pang,W.W., Jaiswal, S., Gibbs, K.D. Jr., van Rooijen, N., and Weissman, I.L. 2009. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 138:286-299.
74. Martin-Castillo, B., Vazquez-Martin, A., Oliveras-Ferraros, C., and Menendez, J.A. 2010. Metformin and cancer: Doses, mechanisms and the dandelion and hormetic phenomena. Cell Cycle 9:1057-1064.
75. Matsui, W., Wang, Q., Barber, J.P., Brennan, S., Smith, B.D., Borrello, I., McNiece, I., Lin, L.,Ambinder, R.F., Peacock, C., Watkins, D.N., Huff, C.A., and Jones, R.J. 2008. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 68:190-197.
76. McCarty, M.F. 2012. Metformin may antagonize Lin28and/or Lin28B activity, thereby boosting let-7 levels and antagonizing cancer progression. Med. Hypotheses 78:262-269.
77. Monami, M., Lamanna, C., Balzi, D., Marchionni, N., and Mannucci, E. 2009. Sulphonylureas and cancer: A case-control study. Acta Diabetol. 46:279-284.
78. Moriyama, T., Ohuchida, K., Mizumoto, K., Yu, J., Sato, N., Nabae, T., Takahata, S., Toma, H., Nagai, E., and Tanaka, M. 2009. MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance. Mol. Cancer Ther. 8:1067-1074.
79. Nalls, D., Tang, S.-N., Rodova, M., Srivastava, R.K., and Shankar, S. 2011. Targeting epigenetic regulation of miR-34a for treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells. PLoS One 6:e24099.
80. Narducci, M.G., Scala, E., Bresin, A., Caprini, E., Picchio, M.C., Remotti, D., Ragone, G., Nasorri, F., Frontani, M., Arcelli, D., Volinia, S., Lombardo, G.A., Baliva, G., Napolitano, M., and Russo, G. 2006. Skin homing of Śezary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV. Blood 107:1108-1115.
81. Nie, Y., Han, B.-M., Liu, X.-B., Yang, J.-J., Wang, F., Cong, X.-F., and Chen, X. 2011. Identification of microRNAs involved in hypoxia- and serum deprivation-induced apoptosis in mesenchymal stem cells. Int. J. Biol. Sci. 7:762-768.
82. Nurwidya, F., Murakami, A., Takahashi, F., and Takahashi, K. 2012. Lung cancer stem cells: Tumor biology and clinical implications. Asia Pac. J. Clin. Oncol. 8:217-22.
83. Olson, P., Lu, J., Zhang, H., Shai, A., Chun, M.G., Wang, Y., Libutti, S.K., Nakakura, E.K., Golub, T.R., and Hanahan, D. 2009. MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes Dev. 23:2152-2165.
84. Pang, Y., Young, C.Y.F., and Yuan, H. 2010. MicroRNAs and prostate cancer. Acta Biochim. Biophys. Sin. 42:363-369.
85. Patrawala, L., Calhoun, T., Schneider-Broussard, R., Zhou, J., Claypool, K., and Tang, D.G. 2005. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res. 65:6207-6219.
86. Patrawala, L., Calhoun-Davis, T., Schneider-Broussard, R., and Tang, D.G. 2007. Hierarchical organization of prostate cancer cells in xenograft tumors: The CD44+α2β1+ cell population is enriched in tumor-initiating cells. Cancer Res. 67:6796-6805.
87. Peter, M.E. 2009. Let-7 and miR-200 microRNAs: Guardians against pluripotency and cancer progression. Cell Cycle 8:843-852.
88. Prud'homme, G.J. 2012. Cancer stem cells and novel targets for antitumor strategies. Curr. Pharm. Des. 18:2838-2849.
89. Rasheed, Z.A. and Matsui, W. 2012. Biological and clinical relevance of stem cells in pancreatic adenocarcinoma. J. Gastroenterol. Hepatol. 27:S15-S18.
90. Regala, R.P., Davis, R.K., Kunz, A., Khoor, A., Leitges, M., and Fields, A.P. 2009. Atypical protein kinase Cι is required for bronchioalveolar stem cell expansion and lung tumorigenesis. Cancer Res. 69:7603-7611.
91. Rozengurt, E., Sinnett-Smith, J., and Kisfalvi, K. 2010. Crosstalk between insulin/insulin-like growth factor-1 receptors andGprotein-coupled receptor signaling systems: A novel target for the antidiabetic drug metformin in pancreatic cancer. Clin. Cancer Res. 16:2505-2511.
92. Sarkar, F.H., Li, Y., Wang, Z., and Kong, D. 2009. Pancreatic cancer stem cells and EMT in drug resistance andmetastasis. MinervaChir. 64:489-500.
93. Shafee, N., Smith, C.R., Wei, S., Kim, Y., Mills, G.B., Hortobagyi, G.N., Stanbridge, E.J., and Lee, E.Y.-H.P. 2008. Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors. Cancer Res. 68:3243-3250.
94. Shaw, R.J., Lamia, K.A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R.A., Montminy, M., and Cantley, L.C. 2005. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310:1642-1646.
95. Shimono, Y., Zabala, M., Cho, R.W., Lobo, N., Dalerba, P., Qian,D., Diehn, M., Liu,H., Panula, S.P., Chiao, E., Dirbas, F.M., Somlo, G., Reijo Pera, R.A., Lao, K., and Clarke, M.F. 2009. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138:592-603.
96. Siegel, R., Naishadham, D., and Jemal, A. 2012. Cancer statistics, 2012. CA Cancer J. Clin. 62:10-29.
97. Sun, F., Fu, H., Liu, Q., Tie, Y., Zhu, J., Xing, R., Sun, Z., and Zheng, X. 2008. Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett. 582:1564-1568.
98. Sun, L., Wu, Z., Shao, Y., Pu, Y., Miu, W., Yao, J., Wu, Y., and Yang, Z. 2012. MicroRNA-34a suppresses cell proliferation and induces apoptosis in U87 glioma stem cells. Technol. Cancer Res. Treat. 11:483-490.
99. Sung, J.-M., Cho, H.-J.,Yi,H., Lee, C.-H., Kim, H.-S., Kim, D.-K., Abd El-Aty, A.M., Kim, J.-S., Landowski,C.P., Hediger,M.A., and Shin, H.-C. 2008. Characterization of a stem cell population in lung cancer A549 cells. Biochem. Biophys. Res. Commun. 371:163-167.
100. Testa, U., Riccioni, R., Diverio, D., Rossini, A., Lo Coco, F., and Peschle, C. 2004. Interleukin-3 receptor in acute leukemia. Leukemia 18:219-226.
101. Toll, A.D., Dasgupta, A., Potoczek, M., Yeo, C.J., Kleer, C.G., Brody, J.R., and Witkiewicz, A.K. 2010. Implications of enhancer of zeste homologue 2 expression in pancreatic ductal adenocarcinoma. Hum. Pathol. 41:1205-1209.
102. Tsujimura, A., Koikawa, Y., Salm, S., Takao, T., Coetzee, S., Moscatelli, D., Shapiro, E., Lepor, H., Sun, T.-T., andWilson, E.L. 2002. Proximal location of mouse prostate epithelial stem cells: A model of prostatic homeostasis. J. Cell Biol. 157:1257-1265.
103. Vazquez-Martin, A., Oliveras-Ferraros, C., Del Barco, S., Martin-Castillo, B., and Menendez, J.A. 2011. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res. Treat. 126:355-364.
104. Wang, X., Meyers, C., Guo, M., and Zheng, Z.-M. 2011. Upregulation of p18Ink4c expression by oncogenic HPV E6 via p53-miR-34a pathway. Int. J. Cancer 129:1362-1372.
105. Warner, J.K.,Wang, J.C.Y., Hope, K.J., Jin, L., and Dick, J.E. 2004. Concepts of human leukemic development. Oncogene 23:7164-7177.
106. Wendlandt, E.B., Graff, J.W., Gioannini, T.L., Mc-Caffrey, A.P., and Wilson, M.E. 2012. The role of microRNAs miR-200b and miR-200c in TLR4 signaling and NF-κB activation. Innate Immun. 18:846-855.
107. Wu,X., Chen,H., andWang, X. 2012. Can lung cancer stem cells be targeted for therapies? Cancer Treat. Rev. 38:580-588.
108. Xin, L., Lawson, D.A., and Witte, O.N. 2005. The Sca-1 cell surface marker enriches for a prostateregenerating cell subpopulation that can initiate prostate tumorigenesis. Proc. Natl. Acad. Sci. U.S.A. 102:6942-6947.
109. Yu, C., Yao, Z., Jiang, Y., and Keller, E.T. 2012. Prostate cancer stem cell biology. Minerva Urol. Nefrol. 64:19-33.
110. Yu, F., Yao, H., Zhu, P., Zhang, X., Pan, Q., Gong, C., Huang, Y., Hu, X., Su, F., Lieberman, J., and Song, E. 2007. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131:1109-1123.
111. Yu, Y., Ramena, G., and Elble, R.C. 2012. The role of cancer stem cells in relapse of solid tumors. Front. Biosci. 4:1528-1541. Zakikhani, M., Dowling, R., Fantus, I.G., Sonenberg, N., and Pollak, M. 2006. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66:10269-10273.
112. Zhang, B., Pan, X., Cobb, G.P., and Anderson, T.A. 2007. microRNAs as oncogenes and tumor suppressors. Dev. Biol. 302:1-12.
113. Zhou, Z., Flesken-Nikitin, A., and Nikitin, A.Yu. 2007. Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of prostatic ducts. Cancer Res. 67:5683-5690.