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The Roles of Epithelial-to-Mesenchymal Transition (EMT) and Mesenchymal-to-Epithelial Transition (MET) in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment

DOI: 10.3390/jcm2040264

Keywords: breast cancer bone metastasis, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), prevention, treatment

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Abstract:

Many studies have revealed molecular connections between breast and bone. Genes, important in the control of bone remodeling, such as receptor activator of nuclear kappa (RANK), receptor activator of nuclear kappa ligand (RANKL), vitamin D, bone sialoprotein (BSP), osteopontin (OPN), and calcitonin, are expressed in breast cancer and lactating breast. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) effectors play critical roles during embryonic development, postnatal growth, and epithelial homeostasis, but also are involved in a number of pathological conditions, including wound repair, fibrosis, inflammation, as well as cancer progression and bone metastasis. Transforming growth factor β (TGFβ), insulin-like growth factor I & II (IGF I & II), platelet-derived growth factor (PDGF), parathyroid hormone-related protein (PTH(rP)), vascular endothelial growth factor (VEGF), epithelial growth factors II/I (ErbB/EGF), interleukin 6 (IL-6), IL-8, IL-11, IL-1, integrin αvβ3, matrix metalloproteinases (MMPs), catepsin K, hypoxia, notch, Wnt, bone morphogenetic proteins (BMP), and hedgehog signaling pathways are important EMT and MET effectors identified in the bone microenviroment facilitating bone metastasis formation. Recently, Runx2, an essential transcription factor in the regulation of mesenchymal cell differentiation into the osteoblast lineage and proper bone development, is also well-recognized for its expression in breast cancer cells promoting osteolytic bone metastasis. Understanding the precise mechanisms of EMT and MET in the pathogenesis of breast cancer bone metastasis can inform the direction of therapeutic intervention and possibly prevention.

References

[1]  Buijs, J.T.; van der Pluijm, G. Osteotropic cancers: From primary tumor to bone. Cancer Lett. 2009, 273, 177–193, doi:10.1016/j.canlet.2008.05.044.
[2]  Sporn, M.B. The war on cancer. Lancet 1996, 347, 1377–1381, doi:10.1016/S0140-6736(96)91015-6.
[3]  Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin. 2011, 61, 69–90, doi:10.3322/caac.20107.
[4]  Sainsbury, R. The development of endocrine therapy for women with breast cancer. Cancer Treat. Rev. 2013, 39, 507–517, doi:10.1016/j.ctrv.2012.07.006.
[5]  Rao, R.D.; Cobleigh, M.A. Adjuvant endocrine therapy for breast cancer. Oncology (Williston Park) 2012, 26, 541–547.
[6]  Hernandez-Aya, L.F.; Gonzalez-Angulo, A.M. Adjuvant systemic therapies in breast cancer. Surg. Clin. North Am. 2013, 93, 473–491, doi:10.1016/j.suc.2012.12.002.
[7]  Vrbic, S.; Pejcic, I.; Filipovic, S.; Kocic, B.; Vrbic, M. Current and future anti-HER2 therapy in breast cancer. J. BUON 2013, 18, 4–16.
[8]  Joerger, M.; Thürlimann, B. Chemotherapy regimens in early breast cancer: Major controversies and future outlook. Expert Rev. Anticancer Ther. 2013, 13, 165–178, doi:10.1586/era.12.172.
[9]  Andre, F.; Dieci, M.V.; Dubsky, P.; Sotiriou, C.; Curigliano, G.; Denkert, C.; Loi, S. Molecular pathways: Involvement of immune pathways in the therapeutic response and outcome in breast cancer. Clin. Cancer Res. 2013, 19, 28–33.
[10]  Coleman, R.E. Skeletal complications of malignancy. Cancer 1997, 80, 1588–1594, doi:10.1002/(SICI)1097-0142(19971015)80:8+<1588::AID-CNCR9>3.0.CO;2-G.
[11]  Steinman, R.A.; Brufsky, A.M.; Oesterreich, S. Zoledronic acid effectiveness against breast cancer metastases—A role for estrogen in the microenvironment? Breast Cancer Res. 2012, 14, doi:10.1186/bcr3223.
[12]  Lipton, A. Future treatment of bone metastases. Clin. Cancer Res. 2006, 12, 6305–6308, doi:10.1158/1078-0432.CCR-06-1157.
[13]  Bouganim, N.; Dranitsaris, G.; Amir, E.; Clemons, M. Optimizing the use of bone-targeted agents in patients with metastatic cancers: A practical guide for medical oncologists. Support. Care Cancer 2011, 19, 1687–1696, doi:10.1007/s00520-011-1230-9.
[14]  Rose, A.A.; Siegel, P.M. Emerging therapeutic targets in breast cancer bone metastases. Future Oncol. 2010, 6, 55–74, doi:10.2217/fon.09.138.
[15]  Lee, B.L.; Higgins, M.J.; Goss, P.E. Denosumab and the current status of bone-modifying drugs in breast cancer. Acta Oncol. 2012, 51, 157–167, doi:10.3109/0284186X.2011.633555.
[16]  Stopeck, A.T.; Lipton, A.; Body, J.J.; Steger, G.G.; Tonkin, K.; de Boer, R.H.; Lichinitser, M.; Fujiwara, Y.; Yardley, D.A.; Viniegra, M.; et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: A randomized, double-blind study. J. Clin. Oncol. 2010, 28, 5132–5139, doi:10.1200/JCO.2010.29.7101.
[17]  Young, R.J.; Coleman, R.E. Zoledronic acid to prevent and treat cancer metastasis: New prospects for an old drug. Future Oncol. 2013, 9, 633–643, doi:10.2217/fon.13.28.
[18]  Casas, A.; Llombart, A.; Martín, M. Denosumab for the treatment of bone metastases in advanced breast cancer. Breast 2013, 22, 585–592, doi:10.1016/j.breast.2013.05.007.
[19]  Chang, J.C.; Wooten, E.C.; Tsimelzon, A.; Hilsenbeck, S.G.; Gutierrez, M.C.; Tham, Y.L.; Kalidas, M.; Elledge, R.; Mohsin, S.; Osborne, C.K.; et al. Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. J. Clin. Oncol. 2005, 23, 169–177.
[20]  Li, X.; Lewis, M.T.; Huang, J.; Gutierrez, C.; Osborne, C.K.; Wu, M.F.; Hilsenbeck, S.G.; Pavlick, A.; Zhang, X.; Chamness, G.C.; et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J. Natl. Cancer Inst. 2008, 100, 672–679, doi:10.1093/jnci/djn123.
[21]  Creighton, C.J.; Li, X.; Landis, M.; Dixon, J.M.; Neumeister, V.M.; Sjolund, A.; Rimm, D.L.; Wong, H.; Rodriguez, A.; Herschkowitz, J.I.; et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc. Natl. Acad. Sci. USA 2009, 106, 13820–13825, doi:10.1073/pnas.0905718106.
[22]  Li, Q.Q.; Xu, J.D.; Wang, W.J.; Cao, X.X.; Chen, Q.; Tang, F.; Chen, Z.Q.; Liu, X.P.; Xu, Z.D. Twist1-mediated adriamycin-induced epithelial mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin. Cancer. Res. 2009, 15, 2657–2665, doi:10.1158/1078-0432.CCR-08-2372.
[23]  Van der Pluijm, G. Epithelial plasticity, cancer stem cells and bone metastasis formation. Bone 2011, 48, 37–43, doi:10.1016/j.bone.2010.07.023.
[24]  Dave, B.; Mittal, V.; Tan, N.M.; Chang, J.C. Epithelial-mesenchymal transition, cancer stem cells and treatment resistance. Breast Cancer Res. 2012, 14, 202.
[25]  Thiery, J.P. Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2002, 2, 442–454, doi:10.1038/nrc822.
[26]  Chambers, A.F.; Groom, A.C.; MacDonald, I.C. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2002, 2, 563–572, doi:10.1038/nrc865.
[27]  Cardiff, R.D.; Couto, S.; Bolon, B. Three interrelated themes in current breast cancer research: Gene addiction, phenotypic plasticity, and cancer stem cells. Breast Cancer Res. 2011, 13, doi:10.1186/bcr2887.
[28]  Takebe, N.; Warren, R.Q.; Ivy, S.P. Breast cancer growth and metastasis: ?nterplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition. Breast Cancer Res. 2011, 13, doi:10.1186/bcr2876.
[29]  Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell 2000, 100, 57–70, doi:10.1016/S0092-8674(00)81683-9.
[30]  Weidner, N.; Folkman, J.; Pozza, F.; Bevilacqua, P.; Allred, E.N.; Moore, D.H.; Meli, S.; Gasparini, G. Tumor angiogenesis: A new significant and independent prognostic indicator in early-stage breast carcinoma. J. Natl. Cancer Inst. 1992, 84, 1875–1887, doi:10.1093/jnci/84.24.1875.
[31]  Folkman, J.; Shing, Y. Angiogenesis. J. Biol. Chem. 1992, 267, 10931–10934.
[32]  Folkman, J. The role of angiogenesis in tumor growth. Semin. Cancer Biol. 1992, 3, 65–71.
[33]  Kiaris, H.; Chatzistamou, I.; Kalofoutis, C.; Koutselini, H.; Piperi, C.; Kalofoutis, A. Tumour-stroma interactions in carcinogenesis: Basic aspects and perspectives. Mol. Cell. Biochem. 2004, 261, 117–122, doi:10.1023/B:MCBI.0000028746.54447.6c.
[34]  Pupa, S.M.; Menard, S.; Forti, S.; Tagliabue, E. New insights into the role of extracellular matrix during tumor onset and progression. J. Cell. Physiol. 2002, 192, 259–267.
[35]  Wells, A.; Chao, Y.L.; Grahovac, J.; Wu, Q.; Lauffenburger, D.A. Epithelial and mesenchymal phenotypic switchings modulate cell motility in metastasis. Front. Biosci. 2011, 16, 815–837, doi:10.2741/3722.
[36]  Mathias, R.A.; Gopala, S.K.; Simpson, R.J. Contribution of cells undergoing epithelial-mesenchymal transition to the tumour microenvironment. J. Proteomics 2013, 78, 545–557, doi:10.1016/j.jprot.2012.10.016.
[37]  Gunasinghe, N.P.A.D.; Wells, A.; Thompson, E.W.; Hugo, H.J. Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer. Cancer Metastasis Rev. 2012, 31, 469–478, doi:10.1007/s10555-012-9377-5.
[38]  Zeisberg, M.; Neilson, E.G. Biomarkers for epithelial-mesenchymal transitions. J. Clin. Invest. 2009, 119, 1429–1437, doi:10.1172/JCI36183.
[39]  Al-Hajj, M.; Wicha, M.S.; Benito-Hernandez, A.; Morrison, S.J.; Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 2003, 100, 3983–3988.
[40]  Blick, T.; Hugo, H.; Widodo, E.; Waltham, M.; Pinto, C.; Mani, S.A.; Weinberg, R.A.; Neve, R.M.; Lenburg, M.E.; Thompson, E.W. Epithelial mesenchymal transition traits in human breast cancer cell lines paralel the CD44 (hi)/CD24 (lo/?) stem cell phenotype in human breast cancer. J. Mammary Gland Biol. Neoplasia 2010, 15, 235–252, doi:10.1007/s10911-010-9175-z.
[41]  Beug, H. Breast cancer stem cells: Eradication by differentiation therapy? Cell 2009, 138, 623–625, doi:10.1016/j.cell.2009.08.007.
[42]  Woelfle, U.; Cloos, J.; Sauter, G.; Riethdorf, L.; Janicke, F.; van Diest, P.; Brakenhoff, R.; Pantel, K. Molecular signature associated with bone marrow micrometastasis in human breast cancer. Cancer Res. 2003, 63, 5679–5684.
[43]  Wang, Y.; Zhou, B.P. Epithelial-mesenchymal transition in breast cancer progression and metastasis. Chin. J. Cancer 2011, 30, 603–611, doi:10.5732/cjc.011.10226.
[44]  Morel, A.P.; Lievre, M.; Thomas, C.; Hinkal, G.; Ansieau, S.; Puisieux, A. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008, 3, e2888.
[45]  Paget, S. The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev. 1989, 8, 98–101.
[46]  Pratap, J.; Lianb, J.B.; Steinb, G.S. Metastatic bone disease: Role of transcription factors and future targets. Bone 2011, 48, 30–36, doi:10.1016/j.bone.2010.05.035.
[47]  Vallone, V.B.F.; Hofer, E.L.; Choi, H.; Bordenave, R.H.; Batagelj, E.; Feldman, L.; La Russa, V.; Caramutti, D.; Dimase, F.; Labovsky, V.; et al. Behaviour of mesenchymal stem cells from bone marrow of untreated advanced breast and lung cancer patients without bone osteolytic metastasis. Clin. Exp. Metastasis 2013, 30, 317–332, doi:10.1007/s10585-012-9539-4.
[48]  Josson, S.; Nomura, T.; Lin, J.-T.; Huang, W.-C.; Wu, D.; Zhau, H.E.; Zayzafoon, M.; Weizmann, M.N.; Gururajan, M.; Chung, L.W.K. Transition and confers cancer lethality and bone β2-microglobulin induces epithelial to mesenchymal metastasis in human cancer cells. Cancer Res. 2011, 71, 2600–2610, doi:10.1158/0008-5472.CAN-10-3382.
[49]  Martin, F.T.; Dwyer, R.M.; Kelly, J.; Khan, S.; Murphy, J.M.; Curran, C.; Miller, N.; Hennessy, E.; Dockery, P.; Barry, F.P.; et al. Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: Stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res. Treat. 2010, 124, 317–326, doi:10.1007/s10549-010-0734-1.
[50]  Jain, V.K.; Turner, N.C. Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer. Breast Cancer Res. 2012, 14, 208, doi:10.1186/bcr3139.
[51]  Martorana, A.M.; Zheng, G.; Crowe, T.C.; O’Grady, R.L.; Lyons, J.G. Epithelial cells up-regulate matrix metalloproteinases in cells within the same mammary carcinoma that have undergone an epithelial-mesenchymal transition. Cancer Res. 1998, 58, 4970–4979.
[52]  Scheel, C.; Eaton, E.N.; Li, S.H.; Chaffer, C.L.; Reinhardt, F.; Kah, K.J.; Bell, G.; Guo, W.; Rubin, J.; Richardson, A.L.; et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell 2011, 145, 926–940, doi:10.1016/j.cell.2011.04.029.
[53]  Boyle, W.J.; Simonet, W.S.; Lacey, D.L. Osteoclast differentiation and activation. Nature 2003, 423, 337–342, doi:10.1038/nature01658.
[54]  Guise, T.A.; Chirgwin, J.M. Transforming growth factor-β in osteolytic breast cancer bone metastases. Clin. Orthop. 2003, 415, 32–38, doi:10.1097/01.blo.0000093055.96273.69.
[55]  Buijs, T.J.; Stayrook, K.R.; Guise, T.A. TGF-β in the bone microenvironment: Role in breast cancer metastases. Cancer Microenviron. 2011, 4, 261–281, doi:10.1007/s12307-011-0075-6.
[56]  Deckers, M.; van Dinther, M.; Buijs, J.; Que, I.; Lowik, C.; van der Pluijm, G.; ten Dijke, P. The tumor suppressor Smad4 is required for transforming growth factor B-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res. 2006, 66, 2202–2209, doi:10.1158/0008-5472.CAN-05-3560.
[57]  Giehl, K.; Imamichib, Y.; Menke, A. Smad4-independent TGF-β signaling in tumor cell migration. Cells Tissues Organs 2007, 185, 123–130, doi:10.1159/000101313.
[58]  Sundqvist, A.; ten Dijke, P.; van Dam, H. Key signaling nodes in mammary gland development and cancer: Smad signal integration in epithelial cell plasticity. Breast Cancer Res. 2012, 14, doi:10.1186/bcr3066.
[59]  Gal, A.; Sjoblom, T.; Fedorova, L.; Imreh, S.; Beug, H.; Moustakas, A. Sustained TGF beta exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis. Oncogene 2008, 27, 1218–1230.
[60]  Roberts, A.B.; Wakefield, L.M. The two faces of transforming growth factor β in carcinogenesis. Proc. Natl. Acad. Sci. USA 2003, 100, 8621–8623, doi:10.1073/pnas.1633291100.
[61]  Ten Dijke, P.; Goumans, M.-J.; Itoh, F.; Itoh, S. Regulation of cell proliferation by Smad proteins. J. Cell. Physiol. 2002, 191, 1–16, doi:10.1002/jcp.10066.
[62]  Yin, J.J.; Selander, K.; Chirgwin, J.M.; Dallas, M.; Grubbs, B.G.; Wieser, R.; Massagué, J.; Mundy, G.R.; Guise, T.A. TGF-β signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J. Clin. Invest. 1999, 103, 197–206, doi:10.1172/JCI3523.
[63]  Tanos, T.; Rojo, L.J.; Echeverria, P.; Brisken, C. ER and PR signaling nodes during mammary gland development. Breast Cancer Res. 2012, 14, doi:10.1186/bcr3166.
[64]  Beleut, M.; Rajaram, R.D.; Caikovski, M.; Ayyanan, A.; Germano, D.; Choi, Y.; Schneider, P.; Brisken, C. Two distinct mechanisms underlie progesterone-induced proliferation in the mammary gland. Proc. Natl. Acad. Sci. USA 2009, 107, 2989–2994.
[65]  Joshi, P.A.; Jackson, H.W.; Beristain, A.G.; di Grappa, M.A.; Mote, P.A.; Clarke, C.L.; Stingl, J.; Waterhouse, P.D.; Khokha, R. Progesterone induces adult mammary stem cell expansion. Nature 2010, 465, 803–807, doi:10.1038/nature09091.
[66]  Asselin-Labat, M.L.; Vaillant, F.; Sheridan, J.M.; Pal, B.; Wu, D.; Simpson, E.R.; Yasuda, H.; Smyth, G.K.; Martin, T.J.; Lindeman, G.J.; et al. Control of mammary stem cell function by steroid hormone signalling. Nature 2010, 465, 798–802, doi:10.1038/nature09027.
[67]  Hinck, L.; Silberstein, G.B. Key stages in mammary gland development: The mammary end bud as a motile organ. Breast Cancer Res. 2005, 7, 245–251, doi:10.1186/bcr1331.
[68]  Tanos, T.; Sflomos, G.; Echeverria, P.C.; Ayyanan, A.; Gutierrez, M.; Delaloye, J.F.; Raffoul, W.; Fiche, M.; Dougall, W.; Schneider, P.;et al. Progesterone/RANKL is a major regulatory axis in the human breast. Sci. Transl. Med. 2013, 5, doi:10.1126/scitranslmed.3005654.
[69]  Ismail, P.M.; DeMayo, F.J.; Amato, P.; Lydon, J.P. Progesterone induction of calcitonin expression in the murine mammary gland. J. Endocrinol. 2004, 180, 287–295, doi:10.1677/joe.0.1800287.
[70]  Andrews, J.L.; Kim, A.C.; Hens, J.R. The role and function of cadherins in the mammary gland. Breast Cancer Res. 2012, 14, doi:10.1186/bcr3065.
[71]  Kowalski, P.J.; Rubin, M.A.; Kleer, C.G. E-Cadherin expression in primary carcinomas of the breast and its distant metastases. Breast Cancer Res. 2003, 5, 217–222, doi:10.1186/bcr651.
[72]  Berx, G.; Staes, K.; van Hengel, J.; Molemans, F.; Bussemakers, M.J.; van Bokhoven, A.; van Roy, F. Cloning and characterization of the human invasion suppressor gene E cadherin (CDH1). Genomics 1995, 26, 281–289, doi:10.1016/0888-7543(95)80212-5.
[73]  Pecina-Slaus, N. Tumor suppressor gene E-cadherin and its role in normal and malignant cells. Cancer Cell Int. 2003, 3, doi:10.1186/1475-2867-3-17.
[74]  Perl, A.K.; Wilgenbus, P.; Dahl, U.; Semb, H.; Christofori, G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 1998, 392, 190–193, doi:10.1038/32433.
[75]  Wells, A.; Yates, C.; Shepard, C.R. E-Cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastatic seeding of disseminated carcinomas. Clin. Exp. Metastasis 2008, 25, 621–628, doi:10.1007/s10585-008-9167-1.
[76]  Saha, B.; Chaiwun, B.; Imam, S.S.; Tsao-Wei, D.D.; Groshen, S.; Naritoku, W.Y.; Imam, S.A. Overexpression of E-cadherin protein in metastatic breast cancer cells in bone. Anticancer Res. 2007, 27, 3903–3908.
[77]  Lehtinen, L.; Ketola, K.; M?kel?, R.; Mpindi, J.P.; Viitala, M.; Kallioniemi, O.; Iljin, K. High-throughput RNAi screening for novel modulators of vimentin expression identifies MTHFD2 as a regulator of breast cancer cell migration and invasion. Oncotarget 2013, 4, 48–63.
[78]  Gregory, P.A.; Bert, A.G.; Paterson, E.L.; Barry, S.C.; Tsykin, A.; Farshid, G.; Vadas, M.A.; Khew-Goodall, Y.; Goodall, G.J. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat. Cell Biol. 2008, 10, 593–601, doi:10.1038/ncb1722.
[79]  Brabletz, S.; Brabletz, T. The ZEB/miR-200 feedback loop—A motor of cellular plasticity in development and cancer? EMBO Rep. 2010, 11, 670–677, doi:10.1038/embor.2010.117.
[80]  Gregory, P.A.; Bracken, C.P.; Smith, E.; Bert, A.G.; Wright, J.A.; Roslan, S.; Morris, M.; Wyatt, L.; Farshid, G.; Lim, Y.Y.; et al. An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol. Biol. Cell 2011, 22, 1686–1698, doi:10.1091/mbc.E11-02-0103.
[81]  Burk, U.; Schubert, J.; Wellner, U.; Schmalhofer, O.; Vincan, E.; Spaderna, S.; Brabletz, T. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008, 9, 582–589, doi:10.1038/embor.2008.74.
[82]  Brabletz, S.; Bajdak, K.; Meidhof, S.; Burk, U.; Niedermann, G.; Firat, E.; Wellner, U.; Dimmler, A.; Faller, G.; Schubert, J.; et al. The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells. EMBO J. 2011, 30, 770–782, doi:10.1038/emboj.2010.349.
[83]  Bullock, M.D.; Sayan, A.E.; Packham, G.K.; Mirnezami, A.H. MicroRNAs: Critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression. Biol. Cell 2012, 104, 3–12, doi:10.1111/boc.201100115.
[84]  Schwarzenbacher, D.; Balic, M.; Pichler, M. The role of microRNAs in breast cancer stem cells. Int. J. Mol. Sci. 2013, 14, 14712–14723, doi:10.3390/ijms140714712.
[85]  Hwang, M.S.; Yu, N.; Stinson, S.Y.; Yue, P.; Newman, R.J.; Allan, B.B.; Dornan, D. miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer. PLoS One 2013, 8, e66502.
[86]  Shimono, Y.; Zabala, M.; Cho, R.W.; Lobo, N.; Dalerba, P.; Qian, D.; Diehn, M.; Liu, H.; Panula, S.P.; Chiao, E.; et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 2009, 138, 592–603, doi:10.1016/j.cell.2009.07.011.
[87]  Ma, L.; Teruya-Feldstein, J.; Weinberg, R.A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007, 449, 682–688, doi:10.1038/nature06174.
[88]  De Herreros, A.G.; Peiro, S.; Nassour, M.; Savagner, P. Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. J. Mammary Gland Biol. Neoplasia 2010, 15, 135–147.
[89]  Maeda, M.; Johnson, K.R.; Wheelock, M.J. Cadherin switching: Essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition. J. Cell Sci. 2005, 118, 873–887, doi:10.1242/jcs.01634.
[90]  Cano, A.; Perez-Moreno, M.A.; Rodrigo, I.; Locascio, A.; Blanco, M.J.; del Barrio, M.G.; Portillo, F.; Nieto, M.A. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol. 2000, 2, 76–83, doi:10.1038/35000025.
[91]  El-Haibia, C.P.; Bellb, G.W.; Zhangc, J.; Collmanna, A.Y.; Woodd, D.; Scherbere, C.M.; Csizmadiaf, E.; Marianig, O.; Zhua, C.; Campagne, A.; et al. Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. PNAS 2012, 109, 17460–17465, doi:10.1073/pnas.1206653109.
[92]  Korpal, M.; Ell, B.J.; Buffa, F.M.; Ibrahim, T.; Blanco, M.A.; Celià-Terrassa, T.; Mercatali, L.; Khan, Z.; Goodarzi, H.; Hua, Y.; et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat. Med. 2011, 17, 1101–1108, doi:10.1038/nm.2401.
[93]  Mathivanan, S.; Ji, H.; Simpson, R.J. Exosomes: Extracellular organelles important in intercellular communication. J. Proteomics 2010, 73, 1907–1920, doi:10.1016/j.jprot.2010.06.006.
[94]  Janowska-Wieczorek, A.; Marquez-Curtis, L.A.; Wysoczynski, M.; Ratajczak, M.Z. Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion 2006, 46, 1199–1209, doi:10.1111/j.1537-2995.2006.00871.x.
[95]  Friel, A.M.; Corcoran, C.; Crown, J.; O’Driscoll, L. Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer. Breast Cancer Res. Treat. 2010, 123, 613–625.
[96]  Simpson, R.J.; Jensen, S.S.; Lim, J.W. Proteomic profiling of exosomes: Current perspectives. Proteomics 2008, 8, 4083–4099, doi:10.1002/pmic.200800109.
[97]  Thery, C.; Zitvogel, L.; Amigorena, S. Exosomes: Composition, biogenesis and function. Nat. Rev. Immunol. 2002, 2, 569–579.
[98]  Katsuno, Y.; Lamouille, S.; Derynck, R. TGF-β signaling and epithelial-mesenchymal transition in cancer progression. Curr. Opin. Oncol. 2013, 25, 76–84, doi:10.1097/CCO.0b013e32835b6371.
[99]  Rappa, G.; Mercapide, J.; Lorico, A. Spontaneous formation of tumorigenic hybrids between breast cancer and multipotent stromal cells is a source of tumor heterogeneity. Am. J. Pathol. 2012, 180, 2504–2515, doi:10.1016/j.ajpath.2012.02.020.
[100]  Sabbah, M.; Emami, S.; Redeuilh, G.; Julien, S.; Prévost, G.; Zimber, A.; Ouelaa, R.; Bracke, M.; de Wever, O.; Gespach, C. Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist. Updat. 2008, 11, 123–151, doi:10.1016/j.drup.2008.07.001.
[101]  Shore, P.A. Role for Runx2 in normal mammary gland and breast cancer bone metastasis. J. Cell. Biochem. 2005, 96, 484–489, doi:10.1002/jcb.20557.
[102]  Pratap, J.; Lian, J.B.; Javed, A.; Barnes, G.L.; van Wijnen, A.J.; Stein, J.L.; Stein, G.S. Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer Metastasis Rev. 2006, 25, 589–600.
[103]  Chimge, N.-O.; Baniwal, S.K.; Little, G.H.; Chen, Y.; Kahn, M.; Tripathy, D.; Borok, Z.; Frenkel, B. Regulation of breast cancer metastasis by Runx2 and estrogen signaling: The role of SNAI2. Breast Cancer Res. 2011, 13, doi:10.1186/bcr3073.
[104]  Mendoza-Villanueva, D.; Zeef, L.; Shore, P. Metastatic breast cancer cells inhibit osteoblast differentiation through the Runx2/CBFb dependent expression of the Wnt antagonist, sclerostin. Breast Cancer Res. 2011, 13, doi:10.1186/bcr3048.
[105]  Katoh, Y.; Katoh, M. Hedgehog signaling, epithelial-to-mesenchymal transition and miRNA. Int. J. Mol. Med. 2008, 22, 271–275.
[106]  Weinberg, R.A. Leaving home early: Reexamination of the canonical models of tumor progression. Cancer Cell 2008, 14, 283–284, doi:10.1016/j.ccr.2008.09.009.
[107]  Scheel, C.; Weinberg, R.A. Cancer stem cells and epithelial-mesenchymal transition: Concepts and molecular links. Semin. Cancer Biol. 2012, 22, 396–403, doi:10.1016/j.semcancer.2012.04.001.
[108]  Yang, J.; Weinberg, R.A. Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis. Dev. Cell 2008, 14, 818–829, doi:10.1016/j.devcel.2008.05.009.
[109]  Foroni, C.; Broggini, M.; Generali, D.; Damia, G. Epithelial-mesenchymal transition and breast cancer: Role, molecular mechanisms and clinical impact. Cancer Treat. Rev. 2012, 38, 689–697, doi:10.1016/j.ctrv.2011.11.001.
[110]  Hennessy, B.T.; Gonzalez-Angulo, A.M.; Stemke-Hale, K.; Gilcrease, M.Z.; Krishnamurthy, S.; Lee, J.S.; Fridlyand, J.; Sahin, A.; Agarwal, R.; Joy, C.; et al. Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res. 2009, 69, 4116–4124, doi:10.1158/0008-5472.CAN-08-3441.
[111]  Howlett, A.R.; Bissell, M.J. The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium. Epithel. Cell Biol. 1993, 2, 79–89.
[112]  Bonnomet, A.; Syne, L.; Brysse, A.; Feyereisen, E.; Thompson, E.W.; Noel, A.; Foidart, J.M.; Birembaut, P.; Polette, M.; Gilles, C. A dynamic in vivo model of epithelial-to-mesenchymal transitions in circulating tumor cells and metastases of breast cancer. Oncogene 2012, 31, 3741–3753.
[113]  Creighton, C.J.; Chang, J.C.; Rosen, J.M. Epithelialmesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer. J. Mammary Gland Biol. Neoplasia 2010, 15, 253–260, doi:10.1007/s10911-010-9173-1.
[114]  Jechlinger, M.; Grunert, S.; Beug, H. Mechanisms in epithelial plasticity and metastasis: Insights from 3D cultures and expression profiling. J. Mammary Gland Biol. Neoplasia 2002, 7, 415–432, doi:10.1023/A:1024090116451.
[115]  Hugo, H.; Ackland, M.L.; Blick, T. Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J. Cell. Physiol. 2007, 213, 374–383, doi:10.1002/jcp.21223.
[116]  Chao, Y.L.; Shepard, C.R.; Wells, A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol. Cancer 2010, 9, doi:10.1186/1476-4598-9-179.
[117]  Patel, S.A.; Dave, M.A.; Murthy, R.G.; Helmy, K.Y.; Rameshwar, P. Metastatic breast cancer cells in the bone marrow microenvironment: Novel insights into oncoprotection. Oncol. Rev. 2011, 5, 93–102, doi:10.1007/s12156-010-0071-y.
[118]  Kallergi, G.; Papadaki, M.A.; Politaki, E.; Mavroudis, D.; Georgoulias, V.; Agelaki, S. Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Res. 2011, 13, doi:10.1186/bcr2896.
[119]  Lopes, N.; Paredes, J.; Costa, J.L.; Ylstra, B.; Schmitt, F. Vitamin D and the mammary gland: A review on its role in normal development and breast cancer. Breast Cancer Res. 2012, 14, doi:10.1186/bcr3178.
[120]  Lopes, N.; Carvalho, J.; Duraes, C.; Sousa, B.; Gomes, M.; Costa, J.L.; Oliveira, C.; Paredes, J.; Schmitt, F. 1Alpha,25-dihydroxyvitamin D3 induces de novo E-cadherin expression in triple-negative breast cancer cells by CDH1-promoter demethylation. Anticancer Res. 2012, 32, 249–257.
[121]  Chao, Y.; Wu, Q.; Acquafondata, M.; Dhir, R.; Wells, A. Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases. Cancer Microenviron. 2012, 5, 19–28, doi:10.1007/s12307-011-0085-4.
[122]  Korpal, M.; Lee, E.S.; Hu, G.; Kang, Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J. Biol. Chem. 2008, 283, 14910–14914, doi:10.1074/jbc.C800074200.
[123]  Park, S.M.; Gaur, A.B.; Lengyel, E.; Peter, M.E. 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, doi:10.1101/gad.1640608.
[124]  Wellner, U.; Schubert, J.; Burk, U.C.; Schmalhofer, O.; Zhu, F.; Sonntag, A.; Waldvogel, B.; Vannier, C.; Darling, D.; zur Hausen, A.; et al. The EMT activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat. Cell Biol. 2009, 11, 1487–1495, doi:10.1038/ncb1998.
[125]  Bracken, C.P.; Gregory, P.A.; Kolesnikoff, N.; Bert, A.G.; Wang, J.; Shannon, M.F.; Goodall, G.J. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 2008, 68, 7846–7854.
[126]  Mani, S.A.; Guo, W.; Liao, M.J.; Eaton, E.N.; Ayyanan, A.; Zhou, A.Y.; Brooks, M.; Reinhard, F.; Zhang, C.C.; Shipitsin, M.; et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133, 704–715, doi:10.1016/j.cell.2008.03.027.
[127]  Drasin, D.J.; Robin, T.P.; Ford, H.L. Breast cancer epithelial-to-mesenchymal transition: Examining the functional consequences of plasticity. Breast Cancer Res. 2011, 13, doi:10.1186/bcr3037.
[128]  Tomaskovic-Crook, E.; Thompson, E.W.; Thiery, J.P. Epithelial to mesenchymal transition and breast cancer. Breast Cancer Res. 2009, 11, doi:10.1186/bcr2416.
[129]  Sas, L.; Lardon, F.; Vermeulen, P.B.; Hauspy, J.; van Dam, P.; Pauwels, P.; Dirix, L.Y.; van Laere, S.J. The interaction between ER and NFκB in resistance to endocrine therapy. Breast Cancer Res. 2012, 14, doi:10.1186/bcr3196.
[130]  Pece, S.; Tosoni, D.; Confalonieri, S.; Mazzarol, G.; Vecchi, M.; Ronzoni, S.; Bernard, L.; Viale, G.; Pelicci, P.G.; di Fiore, P.P. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 2010, 140, 62–73, doi:10.1016/j.cell.2009.12.007.
[131]  Torsvik, A.; Bjerkvig, R. Mesenchymal stem cell signaling in cancer progression. Cancer Treat. Rev. 2013, 39, 180–188.
[132]  Palena, C.; Hamilton, D.H.; Fernando, R.I. Influence of IL-8 on the epithelial-mesenchymal transition and the tumor microenvironment. Future Oncol. 2012, 8, 713–722, doi:10.2217/fon.12.59.
[133]  Buijs, J.T.; Petersen, M.; van der Horst, G.; van der Pluijm, G. Bone morphogenetic proteins and its receptors; therapeutic targets in cancer progression and bone metastasis? Curr. Pharm. Des. 2010, 16, 1291–1300, doi:10.2174/138161210791033987.
[134]  Buijs, J.T.; Henriquez, N.V.; van Overveld, P.G.M.; van der Horst, G.; Que, I.; Schwaninger, R.; Rentsch, C.; ten Dijke, P.; Cleton-Jansen, A.-M.; Driouch, K.; et al. Bone morphogenetic protein 7 in the development and treatment of bone metastases from breast cancer. Cancer Res. 2007, 67, 8742–8751, doi:10.1158/0008-5472.CAN-06-2490.
[135]  Fuxea, J.; Karlsson, M.C.I. TGF-β-induced epithelial-mesenchymal transition: A link between cancer and inflammation. Semin. Cancer Biol. 2012, 22, 455–461, doi:10.1016/j.semcancer.2012.05.004.
[136]  Zheng, Y.; Zhou, H.; Dunstan, C.R.; Sutherland, R.L.; Seibel, M.J. The role of the bone microenvironment in skeletal metastasis. J. Bone Oncol. 2013, 2, 47–57.
[137]  Chirgwin, J.M.; Mohammad, K.S.; Guise, T.A. Tumor-bone cellular interactions in skeletal metastases. J. Musculoskel. Neuron Interact. 2004, 4, 308–318.
[138]  Kozlow, W.; Guise, T.A. Breast cancer metastasis to bone: Mechanisms of osteolysis and implications for therapy. J. Mammary Gland Biol. Neoplasia 2005, 10, 169–180, doi:10.1007/s10911-005-5399-8.
[139]  Kakonen, S.M.; Mundy, G.R. Mechanisms of osteolytic bone metastases in breast carcinoma. Cancer 2003, 97, 834–839, doi:10.1002/cncr.11132.
[140]  Valcourt, U.; Kowanetz, M.; Niimi, H.; Heldin, C.-H.; Moustakas, A. TGF-β and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol. Biol. Cell 2005, 16, 1987–2002, doi:10.1091/mbc.E04-08-0658.
[141]  Kang, Y.; He, W.; Tulley, S.; Gupta, G.P.; Serganova, I.; Chen, C.R.; Manova-Todorova, K.; Blasberg, R.; Gerald, W.L.; Massagué, J. Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proc. Natl. Acad. Sci. USA 2005, 102, 13909–13914.
[142]  Kang, Y.; Siegel, P.M.; Shu, W.; Drobnjak, M.; Kakonen, S.M.; Cordón-Cardo, C.; Guise, T.A.; Massagué, J. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003, 3, 537–549, doi:10.1016/S1535-6108(03)00132-6.
[143]  Sethi, N.; Kang, Y. Notch signaling: Mediator and therapeutic target of bone metastasis. BoneKey Rep. 2012, 1, doi:10.1038/bonekey.2012.2.

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