LIF promotes tumorigenesis and metastasis of breast cancer through the AKT-mTOR pathway

Oncotarget

Volumn 5, Issue 3, 2014, Pages 788-801

  Li, Xiaoyan ^a,b   Yang, Qifeng ^a,b   Yu, Haiyang ^a   Wu, Lihua ^a,c   Zhao, Yuhan ^a   Zhang, Cen ^a   Yue, Xuetian ^a   Liu, Zhen ^a   Wu, Hao ^a   Haffty, Bruce G ^a   Feng, Zhaohui ^a   Hu, Wenwei ^a,d  

^a RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^b SHANDONG UNIVERSITY   (China)

^c ZHEJIANG UNIVERSITY   (China)

^d RUTGERS UNIVERSITY   (United States)

Author keywords

AKT; Breast cancer; LIF; Metastasis; MTOR

Indexed keywords

CYTOKINE; LEUKEMIA INHIBITORY FACTOR; MAMMALIAN TARGET OF RAPAMYCIN; LIF PROTEIN, MOUSE; MTOR PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

ADULT; ARTICLE; BREAST CANCER; CANCER CELL; CANCER GROWTH; CANCER PATIENT; CANCER PROGNOSIS; CARCINOGENESIS; CARCINOGENICITY; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; METASTASIS; RECURRENCE FREE SURVIVAL; ANIMAL; BAGG ALBINO MOUSE; BREAST TUMOR; FEMALE; GENETICS; METABOLISM; MOUSE; NUDE MOUSE; PATHOLOGY; SIGNAL TRANSDUCTION; XENOGRAFT;

ANIMALS; BREAST NEOPLASMS; CARCINOGENESIS; CELL PROLIFERATION; FEMALE; HETEROGRAFTS; HUMANS; LEUKEMIA INHIBITORY FACTOR; MICE; MICE, INBRED BALB C; MICE, NUDE; NEOPLASM METASTASIS; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84896886438     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.1772     Document Type: Article

References (44)

1. Siegel R, Naishadham D and Jemal A. Cancer statistics, 2013. CA: a cancer journal for clinicians. 2013; 63(1):11-30.
2. Nguyen DX, Bos PD and Massague J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009; 9(4):274-284.
3. Gearing DP. The leukemia inhibitory factor and its receptor. Adv Immunol. 1993; 53:31-58.
4. Gearing DP, Druck T, Huebner K, Overhauser J, Gilbert DJ, Copeland NG and Jenkins NA. The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13. Genomics. 1993; 18(1):148-150.
5. Heinrich PC, Behrmann I, Muller-Newen G, Schaper F and Graeve L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 1998; 334 ( Pt 2):297-314.
6. Sasaki N, Shinomi M, Hirano K, Ui-Tei K and Nishihara S. LacdiNAc (GalNAcbeta1-4GlcNAc) contributes to self-renewal of mouse embryonic stem cells by regulating leukemia inhibitory factor/STAT3 signaling. Stem Cells. 2011; 29(4):641-650.
7. Slaets H, Dumont D, Vanderlocht J, Noben JP, Leprince P, Robben J, Hendriks J, Stinissen P and Hellings N. Leukemia inhibitory factor induces an antiapoptotic response in oligodendrocytes through Akt-phosphorylation and up-regulation of 14-3-3. Proteomics. 2008; 8(6):1237-1247.
8. Wysoczynski M, Miekus K, Jankowski K, Wanzeck J, Bertolone S, Janowska-Wieczorek A, Ratajczak J and Ratajczak MZ. Leukemia inhibitory factor: a newly identified metastatic factor in rhabdomyosarcomas. Cancer Res. 2007; 67(5):2131-2140.
9. Freudenberg JM, Ghosh S, Lackford BL, Yellaboina S, Zheng X, Li R, Cuddapah S, Wade PA, Hu G and Jothi R. Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity. Nucleic Acids Res. 2012; 40(8):3364-3377.
10. Arthan D, Hong SK and Park JI. Leukemia inhibitory factor can mediate Ras/Raf/MEK/ERK-induced growth inhibitory signaling in medullary thyroid cancer cells. Cancer Lett. 2010; 297(1):31-41.
11. Kuphal S, Wallner S and Bosserhoff AK. Impact of LIF (leukemia inhibitory factor) expression in malignant melanoma. Exp Mol Pathol. 2013; 95(2):156-165.
12. Guimbaud R, Abitbol V, Bertrand V, Quartier G, Chauvelot-Moachon L, Giroud J, Couturier D and Chaussade DC. Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course. Eur Cytokine Netw. 1998; 9(4):607-612.
13. McKenzie RC and Szepietowski J. Cutaneous leukemia inhibitory factor and its potential role in the development of skin tumors. Dermatol Surg. 2004; 30(2 Pt 2):279-290.
14. Kamohara H, Ogawa M, Ishiko T, Sakamoto K and Baba H. Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression. Int J Oncol. 2007; 30(4):977-983.
15. Garcia-Tunon I, Ricote M, Ruiz A, Fraile B, Paniagua R and Royuela M. OSM, LIF, its receptors, and its relationship with the malignance in human breast carcinoma (in situ and in infiltrative). Cancer Invest. 2008; 26(3):222-229.
16. Fitzgerald JS, Tsareva SA, Poehlmann TG, Berod L, Meissner A, Corvinus FM, Wiederanders B, Pfitzner E, Markert UR and Friedrich K. Leukemia inhibitory factor triggers activation of signal transducer and activator of transcription 3, proliferation, invasiveness, and altered protease expression in choriocarcinoma cells. Int J Biochem Cell Biol. 2005; 37(11):2284-2296.
17. Suman P, Shembekar N and Gupta SK. Leukemia inhibitory factor increases the invasiveness of trophoblastic cells through integrated increase in the expression of adhesion molecules and pappalysin 1 with a concomitant decrease in the expression of tissue inhibitor of matrix metalloproteinases. Fertil Steril. 2013; 99(2):533-542.
18. Maruta S, Takiguchi S, Ueyama M, Kataoka Y, Oda Y, Tsuneyoshi M and Iguchi H. A role for leukemia inhibitory factor in melanoma-induced bone metastasis. Clin Exp Metastasis. 2009; 26(2):133-141.
19. Gearing DP, Gough NM, King JA, Hilton DJ, Nicola NA, Simpson RJ, Nice EC, Kelso A and Metcalf D. Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF). EMBO J. 1987; 6(13):3995-4002.
20. Bay JM, Patterson BK and Teng NN. Leukemia inhibitory factor downregulates human papillomavirus-16 oncogene expression and inhibits the proliferation of cervical carcinoma cells. Infect Dis Obstet Gynecol. 2011; 2011:463081.
21. Starenki D, Singh NK, Jensen DR, Peterson FC and Park JI. Recombinant leukemia inhibitory factor suppresses human medullary thyroid carcinoma cell line xenografts in mice. Cancer Lett. 2013; 339(1):144-151.
22. Zajchowski DA, Bartholdi MF, Gong Y, Webster L, Liu HL, Munishkin A, Beauheim C, Harvey S, Ethier SP and Johnson PH. Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells. Cancer Res. 2001; 61(13):5168-5178.
23. Brown EJ, Beal PA, Keith CT, Chen J, Shin TB and Schreiber SL. Control of p70 s6 kinase by kinase activity of FRAP in vivo. Nature. 1995; 377(6548):441-446.
24. Brunn GJ, Hudson CC, Sekulic A, Williams JM, Hosoi H, Houghton PJ, Lawrence JC, Jr. and Abraham RT. Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science. 1997; 277(5322):99-101.
25. Hay N and Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004; 18(16):1926-1945.
26. Zhou X, Tan M, Stone Hawthorne V, Klos KS, Lan KH, Yang Y, Yang W, Smith TL, Shi D and Yu D. Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res. 2004; 10(20):6779-6788.
27. Ohbayashi N, Ikeda O, Taira N, Yamamoto Y, Muromoto R, Sekine Y, Sugiyama K, Honjoh T and Matsuda T. LIFand IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation. Biol Pharm Bull. 2007; 30(10):1860-1864.
28. Feng Z and Levine AJ. The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein. Trends Cell Biol. 2010; 20(7):427-434.
29. Hu W, Feng Z, Teresky AK and Levine AJ. p53 regulates maternal reproduction through LIF. Nature. 2007; 450(7170):721-724.
30. Kang HJ, Feng Z, Sun Y, Atwal G, Murphy ME, Rebbeck TR, Rosenwaks Z, Levine AJ and Hu W. Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans. Proc Natl Acad Sci U S A. 2009.
31. Feng Z, Zhang C, Kang HJ, Sun Y, Wang H, Naqvi A, Frank AK, Rosenwaks Z, Murphy ME, Levine AJ and Hu W. Regulation of female reproduction by p53 and its family members. FASEB J. 2011; 25(7):2245-2255.
32. Metcalf D. The unsolved enigmas of leukemia inhibitory factor. Stem cells. 2003; 21(1):5-14.
33. Kimber SJ. Leukaemia inhibitory factor in implantation and uterine biology. Reproduction. 2005; 130(2):131-145.
34. Seeliger H, Guba M, Kleespies A, Jauch KW and Bruns CJ. Role of mTOR in solid tumor systems: a therapeutical target against primary tumor growth, metastases, and angiogenesis. Cancer Metastasis Rev. 2007; 26(3-4):611-621.
35. Wander SA, Zhao D, Besser AH, Hong F, Wei J, Ince TA, Milikowski C, Bishopric NH, Minn AJ, Creighton CJ and Slingerland JM. PI3K/mTOR inhibition can impair tumor invasion and metastasis in vivo despite a lack of antiproliferative action in vitro: implications for targeted therapy. Breast Cancer Res Treat. 2013; 138(2):369-381.
36. Gulhati P, Bowen KA, Liu J, Stevens PD, Rychahou PG, Chen M, Lee EY, Weiss HL, O'Connor KL, Gao T and Evers BM. mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Cancer Res. 2011; 71(9):3246-3256.
37. Liu SC, Tsang NM, Chiang WC, Chang KP, Hsueh C, Liang Y, Juang JL, Chow KP and Chang YS. Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance. J Clin Invest. 2013; 123(12):5269-5283.
38. Ramaswamy S, Nakamura N, Vazquez F, Batt DB, Perera S, Roberts TM and Sellers WR. Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci U S A. 1999; 96(5):2110-2115.
39. Feng Z, Zhang H, Levine AJ and Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A. 2005; 102(23):8204-8209.
40. Zheng T, Wang J, Zhao Y, Zhang C, Lin M, Wang X, Yu H, Liu L, Feng Z and Hu W. Spliced MDM2 isoforms promote mutant p53 accumulation and gain-of-function in tumorigenesis. Nature Communications. 2013; 4:2996.
41. Zhang C, Liu J, Liang Y, Wu R, Zhao Y, Hong X, Lin M, Yu H, Liu L, Levine AJ, Hu W and Feng Z. Tumourassociated mutant p53 drives the Warburg effect. Nat Commun. 2013; 4:2935.
42. Yang Q, Moran MS and Haffty BG. Bcl-2 expression predicts local relapse for early-stage breast cancer receiving conserving surgery and radiotherapy. Breast Cancer Res Treat. 2009; 115(2):343-348.
43. Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, Harris L, Hait W and Toppmeyer D. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 2006; 24(36):5652-5657.
44. Hu W, Feng Z, Modica I, Klimstra DS, Song L, Allen PJ, Brennan MF, Levine AJ and Tang LH. Gene Amplifications in Well-Differentiated Pancreatic Neuroendocrine Tumors Inactivate the p53 Pathway. Genes Cancer. 2010; 1(4):360-368.