Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer

Oncotarget

Volumn 7, Issue 34, 2016, Pages 55771-55788

  Deng, Junli ^a,b,c,d   Wang, Li ^c,d   Chen, Hongmin ^c,d   Hao, Jingli ^a,b   Ni, Jie ^a,b   Chang, Lei ^a,b   Duan, Wei ^e   Graham, Peter ^a,b   Li, Yong ^a,b  

^a ST GEORGE HOSPITAL   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

^c Henan Cancer Hospital   (China)

^d ZHENGZHOU UNIVERSITY   (China)

^e DEAKIN UNIVERSITY   (Australia)

Author keywords

Chemoresistance; CSC; EMT; Metastasis; Ovarian cancer; Therapy

Indexed keywords

CARBOPLATIN; CD133 ANTIGEN; CD24 ANTIGEN; CISPLATIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPITHELIAL CELL ADHESION MOLECULE; ETOPOSIDE; IMATINIB; MICRORNA 200; MITOGEN ACTIVATED PROTEIN KINASE; NOTCH3 RECEPTOR; OLAPARIB; PACLITAXEL; PROTEIN P53; STAT3 PROTEIN; STEM CELL FACTOR RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; TUMOR MARKER; ALDEHYDE DEHYDROGENASE; CD24 PROTEIN, HUMAN; CD44 PROTEIN, HUMAN; EPCAM PROTEIN, HUMAN; HYALURONIC ACID BINDING PROTEIN; PROM1 PROTEIN, HUMAN;

ARTICLE; CANCER GROWTH; CANCER MODEL; CANCER RECURRENCE; CANCER RESISTANCE; CANCER STEM CELL; CANCER SURVIVAL; DNA METHYLATION; EPIGENETICS; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; GENE EXPRESSION; HISTONE MODIFICATION; HUMAN; IMMUNOHISTOCHEMISTRY; INTRACELLULAR SIGNALING; METASTASIS; NONHUMAN; OVARY CANCER; PROTEIN EXPRESSION; QUALITY OF LIFE; CHEMISTRY; DRUG EFFECTS; DRUG RESISTANCE; MORTALITY; OVARY TUMOR; PATHOLOGY;

AC133 ANTIGEN; ALDEHYDE DEHYDROGENASE; CD24 ANTIGEN; DRUG RESISTANCE, NEOPLASM; EPITHELIAL CELL ADHESION MOLECULE; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; HUMANS; HYALURONAN RECEPTORS; NEOPLASTIC STEM CELLS; OVARIAN NEOPLASMS;

EID: 84983517632     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9908     Document Type: Article

References (104)

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A. Global cancer statistics, 2012. CA. 2015; 65:87-108.
2. Baldwin LA, Huang B, Miller RW, Tucker T, Goodrich ST, Podzielinski I, DeSimone CP, Ueland FR, van Nagell JR and Seamon LG. Ten-year relative survival for epithelial ovarian cancer. Obstet Gynecol. 2012; 120:612-618.
3. Ozols RF. Treatment goals in ovarian cancer. International journal of gynecological cancer. 2005; 15 Suppl 1:3-11.
4. Davidson B, Trope CG and Reich R. Epithelialmesenchymal transition in ovarian carcinoma. Front Oncol. 2012; 2:33.
5. Marchini S, Fruscio R, Clivio L, Beltrame L, Porcu L, Fuso Nerini I, Cavalieri D, Chiorino G, Cattoretti G, Mangioni C, Milani R, Torri V, Romualdi C, Zambelli A, Romano M, Signorelli M, et al. Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer. Eur J Cancer. 2013; 49:520-530.
6. Steg AD, Bevis KS, Katre AA, Ziebarth A, Dobbin ZC, Alvarez RD, Zhang K, Conner M and Landen CN. Stem cell pathways contribute to clinical chemoresistance in ovarian cancer. Clin Cancer Res. 2012; 18:869-881.
7. Nuti SV, Mor G, Li P and Yin G. TWIST and ovarian cancer stem cells: implications for chemoresistance and metastasis. Oncotarget. 2014; 5:7260-7271. doi: 10.18632/oncotarget.2428.
8. Lamouille S, Xu J and Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014; 15:178-196.
9. Thiery JP, Acloque H, Huang RY and Nieto MA. Epithelialmesenchymal transitions in development and disease. Cell. 2009; 139:871-890.
10. Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest. 2009; 119:1417-1419.
11. Zeisberg M and Neilson EG. Biomarkers for epithelialmesenchymal transitions. J Clin Invest. 2009; 119:1429-1437.
12. Arend RC, Londono-Joshi AI, Straughn JM, Jr. and Buchsbaum DJ. The Wnt/beta-catenin pathway in ovarian cancer: a review. Gynecologic oncology. 2013; 131:772-779.
13. Sabe H. Cancer early dissemination: cancerous epithelialmesenchymal transdifferentiation and transforming growth factor beta signalling. J Biochem. 2011; 149:633-639.
14. Zhang K, Chen D, Jiao X, Zhang S, Liu X, Cao J, Wu L and Wang D. Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling. Lab Invest. 2011; 91:426-438.
15. Vergara D, Merlot B, Lucot JP, Collinet P, Vinatier D, Fournier I and Salzet M. Epithelial-mesenchymal transition in ovarian cancer. Cancer Lett. 2010; 291:59-66.
16. Kajiyama H, Hosono S, Terauchi M, Shibata K, Ino K, Yamamoto E, Nomura S, Nawa A and Kikkawa F. Twist expression predicts poor clinical outcome of patients with clear cell carcinoma of the ovary. Oncology. 2006; 71:394-401.
17. Wang WS, Yu SL, Yang XS, Chang SD and Hou JQ. Expression and significance of twist and E-cadherin in ovarian cancer tissues. Asian Pac J Cancer Prev. 2013; 14:669-672.
18. Takai M, Terai Y, Kawaguchi H, Ashihara K, Fujiwara S, Tanaka T, Tsunetoh S, Tanaka Y, Sasaki H, Kanemura M, Tanabe A and Ohmichi M. The EMT (epithelialmesenchymal-transition)-related protein expression indicates the metastatic status and prognosis in patients with ovarian cancer. J Ovarian Res. 2014; 7:76.
19. Chen D, Wang J, Zhang Y, Chen J, Yang C, Cao W, Zhang H, Liu Y and Dou J. Effect of down-regulated transcriptional repressor ZEB1 on the epithelial-mesenchymal transition of ovarian cancer cells. International journal of gynecological cancer. 2013; 23:1357-1366.
20. Kajiyama H, Shibata K, Terauchi M, Yamashita M, Ino K, Nawa A and Kikkawa F. Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. Int J Oncol. 2007; 31:277-283.
21. LatifiA, Abubaker K, Castrechini N, Ward AC, Liongue C, Dobill F, Kumar J, Thompson EW, Quinn MA, Findlay JK and Ahmed N. Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile. J Cell Biochem. 2011; 112:2850-2864.
22. Rohnalter V, Roth K, Finkernagel F, Adhikary T, Obert J, Dorzweiler K, Bensberg M, Muller-Brusselbach S and Muller R. A multi-stage process including transient polyploidization and EMT precedes the emergence of chemoresistent ovarian carcinoma cells with a dedifferentiated and pro-inflammatory secretory phenotype. Oncotarget. 2015; 6:40005-40025. doi: 10.18632/oncotarget.5552.
23. Haslehurst AM, Koti M, Dharsee M, Nuin P, Evans K, Geraci J, Childs T, Chen J, Li J, Weberpals J, Davey S, Squire J, Park PC and Feilotter H. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC Cancer. 2012; 12:91.
24. Davidson B, Holth A, Hellesylt E, Tan TZ, Huang RY, Trope C, Nesland JM and Thiery JP. The clinical role of epithelial-mesenchymal transition and stem cell markers in advanced-stage ovarian serous carcinoma effusions. Hum Pathol. 2015; 46:1-8.
25. Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY and Bapat SA. Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stemlike phenotype in ovarian cancer cells. Stem Cells. 2009; 27:2059-2068.
26. Yue P, Zhang X, Paladino D, Sengupta B, Ahmad S, Holloway RW, Ingersoll SB and Turkson J. Hyperactive EGF receptor, Jaks and Stat3 signaling promote enhanced colony-forming ability, motility and migration of cisplatinresistant ovarian cancer cells. Oncogene. 2012; 31:2309-2322.
27. Gupta N, Xu Z, El-Sehemy A, Steed H and Fu Y. Notch3 induces epithelial-mesenchymal transition and attenuates carboplatin-induced apoptosis in ovarian cancer cells. Gynecologic oncology. 2013; 130:200-206.
28. Park SM, Gaur AB, Lengyel E and Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008; 22:894-907.
29. Leskela S, Leandro-Garcia LJ, Mendiola M, Barriuso J, Inglada-Perez L, Munoz I, Martinez-Delgado B, Redondo A, de Santiago J, Robledo M, Hardisson D and Rodriguez-Antona C. The miR-200 family controls beta-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients. Endocr Relat Cancer. 2011; 18:85-95.
30. Brozovic A, Duran GE, Wang YC, Francisco EB and Sikic BI. The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells. Mol Oncol. 2015; 9:1678-1693.
31. Du F, Wu X, Liu Y, Wang T, Qi X, Mao Y, Jiang L, Zhu Y, Chen Y, Zhu R, Han X, Jin J, Ma X and Hua D. Acquisition of paclitaxel resistance via PI3Kdependent epithelialmesenchymal transition in A2780 human ovarian cancer cells. Oncol Rep. 2013; 30:1113-1118.
32. Su HY, Lai HC, Lin YW, Liu CY, Chen CK, Chou YC, Lin SP, Lin WC, Lee HY and Yu MH. Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway. Int J Cancer. 2010; 127:555-567.
33. Meng F, Sun G, Zhong M, Yu Y and Brewer MA. Anticancer efficacy of cisplatin and trichostatin A or 5-aza-2'-deoxycytidine on ovarian cancer. Br J Cancer. 2013; 108:579-586.
34. Zhu X, Shen H, Yin X, Long L, Xie C, Liu Y, Hui L, Lin X, Fang Y, Cao Y, Xu Y, Li M, Xu W and Li Y. miR-186 regulation of Twist1 and ovarian cancer sensitivity to cisplatin. Oncogene. 2015.
35. Liu G, Yang D, Rupaimoole R, Pecot CV, Sun Y, Mangala LS, Li X, Ji P, Cogdell D, Hu L, Wang Y, Rodriguez-Aguayo C, Lopez-Berestein G, Shmulevich I, De Cecco L, Chen K, et al. Augmentation of response to chemotherapy by microRNA-506 through regulation of RAD51 in serous ovarian cancers. J Natl Cancer Inst. 2015; 107.
36. Chiu WT, Huang YF, Tsai HY, Chen CC, Chang CH, Huang SC, Hsu KF and Chou CY. FOXM1 confers to epithelialmesenchymal transition, stemness and chemoresistance in epithelial ovarian carcinoma cells. Oncotarget. 2015; 6:2349-2365. doi: 10.18632/oncotarget.2957.
37. Xiong X, Arvizo RR, Saha S, Robertson DJ, McMeekin S, Bhattacharya R and Mukherjee P. Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles. Oncotarget. 2014; 5:6453-6465. doi: 10.18632/oncotarget.2203.
38. Rosano L, Cianfrocca R, Tocci P, Spinella F, Di Castro V, Caprara V, Semprucci E, Ferrandina G, Natali PG and Bagnato A. Endothelin A receptor/beta-arrestin signaling to the Wnt pathway renders ovarian cancer cells resistant to chemotherapy. Cancer research. 2014; 74:7453-7464.
39. Dick JE. Looking ahead in cancer stem cell research. Nat Biotechnol. 2009; 27:44-46.
40. Friedmann-Morvinski D and Verma IM. Dedifferentiation and reprogramming: origins of cancer stem cells. EMBO Rep. 2014; 15:244-253.
41. Dawood S, Austin L and Cristofanilli M. Cancer stem cells: implications for cancer therapy. Oncology (Williston Park). 2014; 28:1101-1107, 1110.
42. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH and Nephew KP. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer research. 2008; 68:4311-4320.
43. Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, Huang Z, Bentley RC, Mori S, Fujii S, Marks JR, Berchuck A and Murphy SK. Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene. 2009; 28:209-218.
44. Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, Roberts DJ, Seiden MV, Scadden DT, Rueda BR and Foster R. CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells. 2009; 27:2875-2883.
45. Bapat SA, Mali AM, Koppikar CB and Kurrey NK. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer research. 2005; 65:3025-3029.
46. Lobo NA, Shimono Y, Qian D and Clarke MF. The biology of cancer stem cells. Annu Rev Cell Dev Biol. 2007; 23:675-699.
47. Goodison S, Urquidi V and Tarin D. CD44 cell adhesion molecules. Mol Pathol. 1999; 52:189-196.
48. Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, Silasi DA, Steffensen KD, Waldstrom M, Visintin I and Mor G. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle. 2009; 8:158-166.
49. Miettinen M and Lasota J. KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol. 2005; 13:205-220.
50. Luo L, Zeng J, Liang B, Zhao Z, Sun L, Cao D, Yang J and Shen K. Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol. 2011; 91:596-602.
51. Chau WK, Ip CK, Mak AS, Lai HC and Wong AS. c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/beta-catenin-ATP-binding cassette G2 signaling. Oncogene. 2013; 32:2767-2781.
52. Neuzil J, Stantic M, Zobalova R, Chladova J, Wang X, Prochazka L, Dong L, Andera L and Ralph SJ. Tumourinitiating cells vs. cancer 'stem' cells and CD133: what's in the name? Biochem Biophys Res Commun. 2007; 355:855-859.
53. Yang CH, Wang HL, Lin YS, Kumar KP, Lin HC, Chang CJ, Lu CC, Huang TT, Martel J, Ojcius DM, Chang YS, Young JD and Lai HC. Identification of CD24 as a cancer stem cell marker in human nasopharyngeal carcinoma. PLoS One. 2014; 9:e99412.
54. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF and Simeone DM. Identification of pancreatic cancer stem cells. Cancer research. 2007; 67:1030-1037.
55. Gao MQ, Choi YP, Kang S, Youn JH and Cho NH. CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene. 2010; 29:2672-2680.
56. Burgos-Ojeda D, Wu R, McLean K, Chen YC, Talpaz M, Yoon E, Cho KR and Buckanovich RJ. CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis. Mol Cancer Ther. 2015; 14:1717-1727.
57. Meng E, Long B, Sullivan P, McClellan S, Finan MA, Reed E, Shevde L and Rocconi RP. CD44+/CD24-ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival. Clin Exp Metastasis. 2012; 29:939-948.
58. Gunjal P, Pedziwiatr D, Ismail AA, Kakar SS and Ratajczak MZ. An emerging question about putative cancer stem cells in established cell lines-are they true stem cells or a fluctuating cell phenotype? Journal of cancer stem cell research. 2015; 3.
59. Marcato P, Dean CA, Giacomantonio CA and Lee PW. Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform. Cell Cycle. 2011; 10:1378-1384.
60. Cheung AM, Wan TS, Leung JC, Chan LY, Huang H, Kwong YL, Liang R and Leung AY. Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential. Leukemia. 2007; 21:1423-1430.
61. Landen CN, Jr., Goodman B, Katre AA, Steg AD, Nick AM, Stone RL, Miller LD, Mejia PV, Jennings NB, Gershenson DM, Bast RC, Jr., Coleman RL, Lopez-Berestein G and Sood AK. Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther. 2010; 9:3186-3199.
62. Silva IA, Bai S, McLean K, Yang K, Griffith K, Thomas D, Ginestier C, Johnston C, Kueck A, Reynolds RK, Wicha MS and Buckanovich RJ. Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer research. 2011; 71:3991-4001.
63. Liu S, Liu C, Min X, Ji Y, Wang N, Liu D, Cai J and Li K. Prognostic value of cancer stem cell marker aldehyde dehydrogenase in ovarian cancer: a meta-analysis. PLoS One. 2013; 8:e81050.
64. Mizuno T, Suzuki N, Makino H, Furui T, Morii E, Aoki H, Kunisada T, Yano M, Kuji S, Hirashima Y, Arakawa A, Nishio S, Ushijima K, Ito K, Itani Y and Morishige K. Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species. Gynecologic oncology. 2015; 137:299-305.
65. Sun Y, Jia X and Wu X. High Expressions of Lgr5 and ALDH1 in Primary Epithelial Ovarian Cancer Correlate with Advanced Tumor Stage and Grade as well as Poor Prognosis of the Patients. Gynecol Obstet Invest. 2015.
66. Munz M, Baeuerle PA and Gires O. The emerging role of EpCAM in cancer and stem cell signaling. Cancer research. 2009; 69:5627-5629.
67. Meirelles K, Benedict LA, Dombkowski D, Pepin D, Preffer FI, Teixeira J, Tanwar PS, Young RH, MacLaughlin DT, Donahoe PK and Wei X. Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance. Proc Natl Acad Sci U S A. 2012; 109:2358-2363.
68. Bellone S, Siegel ER, Cocco E, Cargnelutti M, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S and Santin AD. Overexpression of epithelial cell adhesion molecule in primary, metastatic, and recurrent/chemotherapy-resistant epithelial ovarian cancer: implications for epithelial cell adhesion molecule-specific immunotherapy. International journal of gynecological cancer. 2009; 19:860-866.
69. Boesch M, Zeimet AG, Reimer D, Schmidt S, Gastl G, Parson W, Spoeck F, Hatina J, Wolf D and Sopper S. The side population of ovarian cancer cells defines a heterogeneous compartment exhibiting stem cell characteristics. Oncotarget. 2014; 5:7027-7039. doi: 10.18632/oncotarget.2053.
70. Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, Maclaughlin DT and Donahoe PK. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A. 2006; 103:11154-11159.
71. Liao J, Qian F, Tchabo N, Mhawech-Fauceglia P, Beck A, Qian Z, Wang X, Huss WJ, Lele SB, Morrison CD and Odunsi K. Ovarian cancer spheroid cells with stem celllike properties contribute to tumor generation, metastasis and chemotherapy resistance through hypoxia-resistant metabolism. PLoS One. 2014; 9:e84941.
72. Chang HL, MacLaughlin DT and Donahoe PK. (2008). Somatic stem cells of the ovary and their relationship to human ovarian cancers. StemBook. (Cambridge (MA): Harvard Stem Cell Institute Copyright: (c) 2009 Henry L. Chang, David T. MacLaughlin, and Patricia K. Donahoe.).
73. Wei X, Dombkowski D, Meirelles K, Pieretti-Vanmarcke R, Szotek PP, Chang HL, Preffer FI, Mueller PR, Teixeira J, MacLaughlin DT and Donahoe PK. Mullerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics. Proc Natl Acad Sci U S A. 2010; 107:18874-18879.
74. Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G and Nikitin AY. Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature. 2013; 495:241-245.
75. Yasuda K, Torigoe T, Morita R, Kuroda T, Takahashi A, Matsuzaki J, Kochin V, Asanuma H, Hasegawa T, Saito T, Hirohashi Y and Sato N. Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population. PLoS One. 2013; 8:e68187.
76. Kobayashi Y, Seino K, Hosonuma S, Ohara T, Itamochi H, Isonishi S, Kita T, Wada H, Kojo S and Kiguchi K. Side population is increased in paclitaxel-resistant ovarian cancer cell lines regardless of resistance to cisplatin. Gynecologic oncology. 2011; 121:390-394.
77. Frank NY, Schatton T and Frank MH. The therapeutic promise of the cancer stem cell concept. J Clin Invest. 2010; 120:41-50.
78. Kong D, Li Y, Wang Z and Sarkar FH. Cancer Stem Cells and Epithelial-to-Mesenchymal Transition (EMT)-Phenotypic Cells: Are They Cousins or Twins? Cancers (Basel). 2011; 3:716-729.
79. Bonneau C, Rouzier R, Geyl C, Cortez A, Castela M, Lis R, Darai E and Touboul C. Predictive markers of chemoresistance in advanced stages epithelial ovarian carcinoma. Gynecologic oncology. 2015; 136:112-120.
80. Gao Y, Foster R, Yang X, Feng Y, Shen JK, Mankin HJ, Hornicek FJ, Amiji MM and Duan Z. Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer. Oncotarget. 2015; 6:9313-9326. doi: 10.18632/oncotarget.3220.
81. Zhang J, Guo X, Chang DY, Rosen DG, Mercado-Uribe I and Liu J. CD133 expression associated with poor prognosis in ovarian cancer. Mod Pathol. 2012; 25:456-464.
82. Štemberger-Papi S. Expression of CD 133 and CD 117 in 64 Serous Ovarian Cancer Cases. Coll Antropol. 2015; 39:745-753.
83. Zhu J, Zhang G and Lu H. CD24, COX-2, and p53 in epithelial ovarian cancer and its clinical significance. Front Biosci (Elite Ed). 2012; 4:2745-2751.
84. Cole JM, Joseph S, Sudhahar CG and Cowden Dahl KD. Enrichment for chemoresistant ovarian cancer stem cells from human cell lines. J Vis Exp. 2014;:51891.
85. Abubaker K, Luwor RB, Escalona R, McNally O, Quinn MA, Thompson EW, Findlay JK and Ahmed N. Targeted Disruption of the JAK2/STAT3 Pathway in Combination with Systemic Administration of Paclitaxel Inhibits the Priming of Ovarian Cancer Stem Cells Leading to a Reduced Tumor Burden. Front Oncol. 2014; 4:75.
86. Kwon MJ and Shin YK. Regulation of ovarian cancer stem cells or tumor-initiating cells. Int J Mol Sci. 2013; 14:6624-6648.
87. Abubaker K, LatifiA, Luwor R, Nazaretian S, Zhu H, Quinn MA, Thompson EW, Findlay JK and Ahmed N. Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden. Mol Cancer. 2013; 12:24.
88. Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW and Holland EC. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell stem cell. 2009; 4:226-235.
89. Ricci F, Bernasconi S, Perego P, Ganzinelli M, Russo G, Bono F, Mangioni C, Fruscio R, Signorelli M, Broggini M and Damia G. Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype. Cell Cycle. 2012; 11:1966-1976.
90. Kruger JA, Kaplan CD, Luo Y, Zhou H, Markowitz D, Xiang R and Reisfeld RA. Characterization of stem celllike cancer cells in immune-competent mice. Blood. 2006; 108:3906-3912.
91. Srivastava AK, Han C, Zhao R, Cui T, Dai Y, Mao C, Zhao W, Zhang X, Yu J and Wang QE. Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells. Proc Natl Acad Sci U S A. 2015; 112:4411-4416.
92. Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V, Liang M, RomanoffE, Bingham J, Garofalo F, Alvero A and Mor G. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene. 2015; 34:3605-3616.
93. Juretzka M, Hensley ML, Tew W, Konner J, Aghajanian C, Leitao M, Iasonos A, Soslow R, Park K and Sabbatini P. A phase 2 trial of oral imatinib in patients with epithelial ovarian, fallopian tube, or peritoneal carcinoma in second or greater remission. European journal of gynaecological oncology. 2008; 29:568-572.
94. Schilder RJ, Sill MW, Lee RB, Shaw TJ, Senterman MK, Klein-Szanto AJ, Miner Z and Vanderhyden BC. Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group Study. Journal of clinical oncology. 2008; 26:3418-3425.
95. Coleman RL, Broaddus RR, Bodurka DC, Wolf JK, Burke TW, Kavanagh JJ, Levenback CF and Gershenson DM. Phase II trial of imatinib mesylate in patients with recurrent platinum-and taxane-resistant epithelial ovarian and primary peritoneal cancers. Gynecologic oncology. 2006; 101:126-131.
96. Alberts DS, Liu PY, Wilczynski SP, Jang A, Moon J, Ward JH, Beck JT, Clouser M and Markman M. Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211). International journal of gynecological cancer. 2007; 17:784-788.
97. Skubitz AP, Taras EP, Boylan KL, Waldron NN, Oh S, Panoskaltsis-Mortari A and Vallera DA. Targeting CD133 in an in vivo ovarian cancer model reduces ovarian cancer progression. Gynecologic oncology. 2013; 130:579-587.
98. Kolev VN, Wright QG, Vidal CM, Ring JE, Shapiro IM, Ricono J, Weaver DT, Padval MV, Pachter JA and Xu Q. PI3K/mTOR dual inhibitor VS-5584 preferentially targets cancer stem cells. Cancer research. 2015; 75:446-455.
99. Zucha MA, Wu AT, Lee WH, Wang LS, Lin WW, Yuan CC and Yeh CT. Bruton's tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer. Oncotarget. 2015; 6:13255-13268. doi: 10.18632/oncotarget.3658.
100. McAuliffe SM, Morgan SL, Wyant GA, Tran LT, Muto KW, Chen YS, Chin KT, Partridge JC, Poole BB, Cheng KH, Daggett J, Jr., Cullen K, KantoffE, Hasselbatt K, Berkowitz J, Muto MG, et al. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proc Natl Acad Sci U S A. 2012; 109:E2939-2948.
101. Wang Y, Cardenas H, Fang F, Condello S, Taverna P, Segar M, Liu Y, Nephew KP and Matei D. Epigenetic targeting of ovarian cancer stem cells. Cancer research. 2014; 74:4922-4936.
102. Wu YH, Chiu WT, Young MJ, Chang TH, Huang YF and Chou CY. Solanum Incanum Extract Downregulates Aldehyde Dehydrogenase 1-Mediated Stemness and Inhibits Tumor Formation in Ovarian Cancer Cells. J Cancer. 2015; 6:1011-1019.
103. Shigdar S, Qiao L, Zhou SF, Xiang D, Wang T, Li Y, Lim LY, Kong L, Li L and Duan W. RNA aptamers targeting cancer stem cell marker CD133. Cancer Lett. 2013; 330:84-95.
104. Wang T, Gantier MP, Xiang D, Bean AG, Bruce M, Zhou SF, Khasraw M, Ward A, Wang L, Wei MQ, AlShamaileh H, Chen L, She X, Lin J, Kong L, Shigdar S, et al. EpCAM Aptamer-mediated Survivin Silencing Sensitized Cancer Stem Cells to Doxorubicin in a Breast Cancer Model. Theranostics. 2015; 5:1456-1472.