An integrated genomic approach identifies that the PI3K/AKT/FOXO pathway is involved in breast cancer tumor initiation

Oncotarget

Volumn 7, Issue 3, 2016, Pages 2596-2610

  Smit, Linda ^a,e   Berns, Katrien ^a   Spence, Katherine ^b   David Ryder, W ^c   Zeps, Nik ^d   Madiredjo, Mandy ^a   Beijersbergen, Roderick ^a   Bernards, René ^a   Clarke, Robert B ^b  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c CHRISTIE HOSPITAL   (United Kingdom)

^d St John of God Subiaco Hospital   (Australia)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

AKT; Breast cancer; FOXO; Genetic screen; Stem cells

Indexed keywords

CD133 ANTIGEN; CD24 ANTIGEN; CELL MARKER; NOTCH RECEPTOR; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SHORT HAIRPIN RNA; TRANSCRIPTION FACTOR FOXO; FOXO3 PROTEIN, HUMAN; MESSENGER RNA; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR FKHRL1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BREAST CARCINOGENESIS; BREAST CELL; CANCER RECURRENCE; CANCER RESISTANCE; CELL DIFFERENTIATION; CONTROLLED STUDY; DOWN REGULATION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE IDENTIFICATION; GENETIC REGULATION; GENETIC SCREENING; MAMMOSPHERE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BREAST TUMOR; CANCER STEM CELL; CELL PROLIFERATION; CELL TRANSFORMATION; FEMALE; GENETICS; GENOMICS; HUMAN; MAMMARY GLAND; METABOLISM; NONOBESE DIABETIC MOUSE; PATHOLOGY; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCID MOUSE; TUMOR CELL CULTURE; TUMOR RECURRENCE; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; BREAST NEOPLASMS; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; FEMALE; FORKHEAD BOX PROTEIN O3; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GENOMICS; HUMANS; MAMMARY GLANDS, HUMAN; MICE; MICE, INBRED NOD; MICE, SCID; NEOPLASM RECURRENCE, LOCAL; NEOPLASTIC STEM CELLS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; RNA, SMALL INTERFERING; TUMOR CELLS, CULTURED;

EID: 84962251554     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.6354     Document Type: Article

References (56)

1. Jordan CT, Guzman ML and Noble M. Cancer stem cells. The New England journal of medicine. 2006; 355:1253-1261.
2. Reya T, Morrison SJ, Clarke MF and Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001; 414:105-111.
3. Calcagno AM, Salcido CD, Gillet JP, Wu CP, Fostel JM, Mumau MD, Gottesman MM, Varticovski L and Ambudkar SV. Prolonged drug selection of breast cancer cells and enrichment of cancer stem cell characteristics. Journal of the National Cancer Institute. 2010; 102:1637-1652.
4. Lacerda L, Pusztai L and Woodward WA. The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches. Drug resistance updates: reviews and commentaries in antimicrobial and anticancer chemotherapy. 2010; 13:99-108.
5. Mao J, Song B, Shi Y, Wang B, Fan S, Yu X, Tang J and Li L. ShRNA targeting Notch1 sensitizes breast cancer stem cell to paclitaxel. The international journal of biochemistry & cell biology. 2013; 45:1064-1073.
6. Bonnet D and Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature medicine. 1997; 3:730-737.
7. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America. 2003; 100:3983-3988.
8. O'Brien CA, Pollett A, Gallinger S and Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007; 445:106-110.
9. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007; 445:111-115.
10. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD and Dirks PB. Identification of human brain tumour initiating cells. Nature. 2004; 432:396-401.
11. Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM and Wicha MS. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast cancer research: BCR. 2004; 6:R605-615.
12. Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, Bundred NJ and Clarke RB. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer research. 2010; 70:709-718.
13. Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, Suri P and Wicha MS. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer research. 2006; 66:6063-6071.
14. Lamb R, Ablett MP, Spence K, Landberg G, Sims AH and Clarke RB. Wnt pathway activity in breast cancer sub-types and stem-like cells. PloS one. 2013; 8:e67811.
15. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ and Wicha MS. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes & development. 2003; 17:1253-1270.
16. Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson NG and Bundred NJ. Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways. Journal of the National Cancer Institute. 2007; 99:616-627.
17. Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA and Daidone MG. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer research. 2005; 65:5506-5511.
18. Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, Brown M, Viens P, Xerri L, Bertucci F, Stassi G, Dontu G, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer research. 2009; 69:1302-1313.
19. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS and Dontu G. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell stem cell. 2007; 1:555-567.
20. Meyer MJ, Fleming JM, Lin AF, Hussnain SA, Ginsburg E and Vonderhaar BK. CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer. Cancer research. 2010; 70:4624-4633.
21. O'Brien CA, Kreso A and Dick JE. Cancer stem cells in solid tumors: an overview. Seminars in radiation oncology. 2009; 19:71-77.
22. Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K and Tang DG. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2-cancer cells are similarly tumorigenic. Cancer research. 2005; 65:6207-6219.
23. Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV and Varticovski L. Brca1 breast tumors contain distinct CD44+/CD24-and CD133+ cells with cancer stem cell characteristics. Breast cancer research: BCR. 2008; 10:R10.
24. Aomatsu N, Yashiro M, Kashiwagi S, Takashima T, Ishikawa T, Ohsawa M, Wakasa K and Hirakawa K. CD133 is a useful surrogate marker for predicting chemosensitivity to neoadjuvant chemotherapy in breast cancer. PloS one. 2012; 7:e45865.
25. Li SY, Rong M, Grieu F and Iacopetta B. PIK3CA mutations in breast cancer are associated with poor outcome. Breast cancer research and treatment. 2006; 96:91-95.
26. Perez-Tenorio G and Stal O. Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. British journal of cancer. 2002; 86:540-545.
27. Baselga J. Targeting the phosphoinositide-3 (PI3) kinase pathway in breast cancer. The oncologist. 2011; 16 Suppl 1:12-19.
28. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, van de Vijver MJ and Bernards R. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer cell. 2007; 12:395-402.
29. Singh JK, Farnie G, Bundred NJ, Simoes BM, Shergill A, Landberg G, Howell SJ and Clarke RB. Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and increases the efficacy of inhibiting HER2 via HER2-dependent and-independent mechanisms. Clinical cancer research: an official journal of the American Association for Cancer Research. 2013; 19:643-656.
30. Greer EL and Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene. 2005; 24:7410-7425.
31. Hu MC, Lee DF, Xia W, Golfman LS, Ou-Yang F, Yang JY, Zou Y, Bao S, Hanada N, Saso H, Kobayashi R and Hung MC. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell. 2004; 117:225-237.
32. Modur V, Nagarajan R, Evers BM and Milbrandt J. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. The Journal of biological chemistry. 2002; 277:47928-47937.
33. Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M, Kerkhoven RM, Madiredjo M, Nijkamp W, Weigelt B, Agami R, Ge W, Cavet G, Linsley PS, Beijersbergen RL and Bernards R. A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature. 2004; 428:431-437.
34. Habashy HO, Rakha EA, Aleskandarany M, Ahmed MA, Green AR, Ellis IO and Powe DG. FOXO3a nuclear localisation is associated with good prognosis in luminallike breast cancer. Breast cancer research and treatment. 2011; 129:11-21.
35. Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, Clouthier SG and Wicha MS. Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS biology. 2009; 7:e1000121.
36. McClements L, Yakkundi A, Papaspyropoulos A, Harrison H, Ablett MP, Jithesh PV, McKeen HD, Bennett R, Donley C, Kissenpfennig A, McIntosh S, McCarthy HO, O'Neill E, Clarke RB and Robson T. Targeting treatment-resistant breast cancer stem cells with FKBPL and its peptide derivative, AD-01, via the CD44 pathway. Clinical cancer research: an official journal of the American Association for Cancer Research. 2013; 19:3881-3893.
37. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J and Greenberg ME. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999; 96:857-868.
38. Medema RH, Kops GJ, Bos JL and Burgering BM. AFXlike Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 2000; 404:782-787.
39. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J and Song E. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007; 131:1109-1123.
40. Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J and Chang JC. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. Journal of the National Cancer Institute. 2008; 100:672-679.
41. Phillips TM, McBride WH and Pajonk F. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. Journal of the National Cancer Institute. 2006; 98:1777-1785.
42. Simoes BM, O'Brien CS, Eyre R, Silva A, Yu L, Sarmiento-Castro A, Alferez DG, Spence K, Santiago-Gomez A, Chemi F, Acar A, Gandhi A, Howell A, Brennan K, Ryden L, Catalano S, et al. Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity. Cell reports. 2015; 12:1968-1977.
43. Charafe-Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B, Houvenaeghel G, Extra JM, Bertucci F, Jacquemier J, Xerri L, Dontu G, Stassi G, Xiao Y, Barsky SH, Birnbaum D, et al. Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 2010; 16:45-55.
44. Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, Garcia-Echeverria C, Schultz PG and Reddy VA. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106:268-273.
45. Sunayama J, Sato A, Matsuda K, Tachibana K, Watanabe E, Seino S, Suzuki K, Narita Y, Shibui S, Sakurada K, Kayama T, Tomiyama A and Kitanaka C. FoxO3a functions as a key integrator of cellular signals that control glioblastoma stem-like cell differentiation and tumorigenicity. Stem cells (Dayton, Ohio). 2011; 29:1327-1337.
46. Ning Y, Luo C, Ren K, Quan M and Cao J. FOXO3amediated suppression of the self-renewal capacity of sphere-forming cells derived from the ovarian cancer SKOV3 cell line by 7-difluoromethoxyl-5, 4'-di-n-octyl genistein. Molecular medicine reports. 2014; 9:1982-1988.
47. Prabhu VV, Allen JE, Dicker DT and El-Deiry WS. Small-Molecule ONC201/TIC10 Targets Chemotherapy-Resistant Colorectal Cancer Stem-like Cells in an Akt/Foxo3a/TRAIL-Dependent Manner. Cancer research. 2015; 75:1423-1432.
48. Zhou Y, Liang C, Xue F, Chen W, Zhi X, Feng X, Bai X and Liang T. Salinomycin decreases doxorubicin resistance in hepatocellular carcinoma cells by inhibiting the betacatenin/TCF complex association via FOXO3a activation. Oncotarget. 2015; 6:10350-10365. doi: 10.18632/oncotarget.3585
49. Naka K, Hoshii T, Muraguchi T, Tadokoro Y, Ooshio T, Kondo Y, Nakao S, Motoyama N and Hirao A. TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature. 2010; 463:676-680.
50. Renault VM, Rafalski VA, Morgan AA, Salih DA, Brett JO, Webb AE, Villeda SA, Thekkat PU, Guillerey C, Denko NC, Palmer TD, Butte AJ and Brunet A. FoxO3 regulates neural stem cell homeostasis. Cell stem cell. 2009; 5:527-539.
51. Santamaria CM, Chillon MC, Garcia-Sanz R, Perez C, Caballero MD, Ramos F, de Coca AG, Alonso JM, Giraldo P, Bernal T, Queizan JA, Rodriguez JN, Fernandez-Abellan P, Barez A, Penarrubia MJ, Vidriales MB, et al. High FOXO3a expression is associated with a poorer prognosis in AML with normal cytogenetics. Leukemia research. 2009; 33:1706-1709.
52. Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, Guan JL, Dontu G and Wicha MS. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. The Journal of clinical investigation. 2010; 120:485-497.
53. Chakrabarty A, Bhola NE, Sutton C, Ghosh R, Kuba MG, Dave B, Chang JC and Arteaga CL. Trastuzumabresistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors. Cancer research. 2013; 73:1190-1200.
54. Mendelsohn J and Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene. 2000; 19:6550-6565.
55. Marte BM, Meyer T, Stabel S, Standke GJ, Jaken S, Fabbro D and Hynes NE. Protein kinase C and mammary cell differentiation: involvement of protein kinase C alpha in the induction of beta-casein expression. Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research. 1994; 5:239-247.
56. Nguyen Huu NS, Ryder WD, Zeps N, Flasza M, Chiu M, Hanby AM, Poulsom R, Clarke RB and Baron M. Tumourpromoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator. The Journal of pathology. 2008; 216:93-102.