TGFΒ-induced transcription in cancer

Seminars in Cancer Biology - Tập 42 - Trang 60-69 - 2017
Gaia Cantelli1, Eva Crosas-Molist1, Mirella Georgouli1, Victoria Sanz-Moreno1
1Tumour Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London, London SE1 1UL, UK

Tài liệu tham khảo

Heldin, 2012, Regulation of EMT by TGFbeta in cancer, FEBS Lett., 586, 1959, 10.1016/j.febslet.2012.02.037 Moses, 1990, TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights, Cell, 63, 245, 10.1016/0092-8674(90)90155-8 Loomans, 2014, Intertwining of activin a and TGFbeta signaling: dual roles in cancer progression and cancer cell invasion, Cancers, 7, 70, 10.3390/cancers7010070 Drabsch, 2012, TGF-beta signalling and its role in cancer progression and metastasis, Cancer Metastasis Rev., 31, 553, 10.1007/s10555-012-9375-7 Morrison, 2013, The relevance of the TGF-beta paradox to EMT-MET programs, Cancer Lett., 341, 30, 10.1016/j.canlet.2013.02.048 Nakao, 1997, TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4, EMBO J., 16, 5353, 10.1093/emboj/16.17.5353 Abdollah, 1997, TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling, J. Biol. Chem., 272, 27678, 10.1074/jbc.272.44.27678 Massague, 2012, TGFbeta signalling in context, Nat. Rev. Mol. Cell Biol., 13, 616, 10.1038/nrm3434 Fleming, 2009, TGF-beta-mediated activation of RhoA signalling is required for efficient (V12)HaRas and (V600E)BRAF transformation, Oncogene, 28, 983, 10.1038/onc.2008.449 Bhowmick, 2001, Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism, Mol. Biol. Cell, 12, 27, 10.1091/mbc.12.1.27 Lu, 2007, Dose-dependent cross-talk between the transforming growth factor-beta and interleukin-1 signaling pathways, Proc. Natl. Acad. Sci. U. S. A., 104, 4365, 10.1073/pnas.0700118104 Ozdamar, 2005, Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity, Science, 307, 1603, 10.1126/science.1105718 Foletta, 2003, Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1, J. Cell Biol., 162, 1089, 10.1083/jcb.200212060 Siegel, 2013, Cancer statistics, 2013, CA: Cancer J. Clin., 63, 11 Tian, 2011, Transforming growth factor-beta and the hallmarks of cancer, Cell. Signal., 23, 951, 10.1016/j.cellsig.2010.10.015 Massague, 2008, TGFbeta in cancer, Cell, 134, 215, 10.1016/j.cell.2008.07.001 Fabregat, 2014, TGF-beta signaling in cancer treatment, Curr. Pharm. Des., 20, 2934, 10.2174/13816128113199990591 Levy, 2006, Alterations in components of the TGF-beta superfamily signaling pathways in human cancer, Cytokine Growth Factor Rev., 17, 41, 10.1016/j.cytogfr.2005.09.009 O'Leary, 2015, Identification of Endoglin as an epigenetically regulated tumour-suppressor gene in lung cancer, Br. J. Cancer, 113, 970, 10.1038/bjc.2015.302 Ji, 2015, Mutant p53 promotes tumor cell malignancy by both positive and negative regulation of the transforming growth factor beta (TGF-beta) pathway, J. Biol. Chem., 290, 11729, 10.1074/jbc.M115.639351 Kuo, 2015, Epigenetic inactivation of transforming growth factor-beta1 target gene HEYL, a novel tumor suppressor, is involved in the P53-induced apoptotic pathway in hepatocellular carcinoma, Hepatol. Res., 45, 782, 10.1111/hepr.12414 Sato, 2014, An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-beta in human breast cancer, Breast Cancer Res.: BCR, 16, R57, 10.1186/bcr3668 Ciftci, 2014, High serum transforming growth factor beta 1 (TGFB1) level predicts better survival in breast cancer, Tumour Biol., 35, 6941, 10.1007/s13277-014-1932-y Lee, 2014, Ahnak functions as a tumor suppressor via modulation of TGFbeta/Smad signaling pathway, Oncogene, 33, 4675, 10.1038/onc.2014.69 Agajanian, 2015, PEAK1 acts as a molecular switch to regulate context-dependent TGFbeta responses in breast cancer, PLoS One, 10, e0135748, 10.1371/journal.pone.0135748 Dimberg, 2010, Chemokines in angiogenesis, Curr. Top. Microbiol. Immunol., 341, 59 Bhowmick, 2004, TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia, Science, 303, 848, 10.1126/science.1090922 Lebrin, 2005, TGF-beta receptor function in the endothelium, Cardiovasc. Res., 65, 599, 10.1016/j.cardiores.2004.10.036 Tang, 2015, Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis, Nat. Commun., 6, 8230, 10.1038/ncomms9230 Mazzocca, 2009, Inhibition of transforming growth factor beta receptor I kinase blocks hepatocellular carcinoma growth through neo-angiogenesis regulation, Hepatology, 50, 1140, 10.1002/hep.23118 Mazzocca, 2010, Down-regulation of connective tissue growth factor by inhibition of transforming growth factor beta blocks the tumor-stroma cross-talk and tumor progression in hepatocellular carcinoma, Hepatology, 51, 523, 10.1002/hep.23285 Mirzoeva, 2014, Apigenin inhibits TGF-beta-induced VEGF expression in human prostate carcinoma cells via a Smad2/3- and Src-dependent mechanism, Mol. Carcinog., 53, 598, 10.1002/mc.22005 Seystahl, 2015, Differential regulation of TGF-beta-induced, ALK-5-mediated VEGF release by SMAD2/3 versus SMAD1/5/8 signaling in glioblastoma, Neuro Oncol., 17, 254, 10.1093/neuonc/nou218 Pham, 2015, VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFbetaR signaling-dependent manner, Cancer Lett., 360, 60, 10.1016/j.canlet.2015.02.005 Pen, 2008, Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2-dependent TGF-beta signaling, Oncogene, 27, 6834, 10.1038/onc.2008.287 Schulte, 2013, Cadherin-11 regulates motility in normal cortical neural precursors and glioblastoma, PLoS One, 8, e70962, 10.1371/journal.pone.0070962 Liu, 2005, Selective induction of interleukin-8 expression in metastatic melanoma cells by transforming growth factor-beta 1, Cytokine, 31, 241, 10.1016/j.cyto.2005.03.008 Lamouille, 2014, Molecular mechanisms of epithelial-mesenchymal transition, Nat. Rev. Mol. Cell Biol., 15, 178, 10.1038/nrm3758 Bierie, 2006, Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer, Nat. Rev. Cancer, 6, 506, 10.1038/nrc1926 Cirri, 2012, Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression, Cancer Metastasis Rev., 31, 195, 10.1007/s10555-011-9340-x Kalluri, 2006, Fibroblasts in cancer, Nat. Rev. Cancer, 6, 392, 10.1038/nrc1877 Yu, 2000, Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis, Genes Dev., 14, 163, 10.1101/gad.14.2.163 Lynch, 2002, Matrix metalloproteinases in tumor-host cell communication, Differentiation, 70, 561, 10.1046/j.1432-0436.2002.700909.x Eck, 2009, CXCR4 and matrix metalloproteinase-1 are elevated in breast carcinoma-associated fibroblasts and in normal mammary fibroblasts exposed to factors secreted by breast cancer cells, Mol. Cancer Res., 7, 1033, 10.1158/1541-7786.MCR-09-0015 Calon, 2012, Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation, Cancer Cell, 22, 571, 10.1016/j.ccr.2012.08.013 De Wever, 2004, Critical role of N-cadherin in myofibroblast invasion and migration in vitro stimulated by colon-cancer-cell-derived TGF-beta or wounding, J. Cell Sci., 117, 4691, 10.1242/jcs.01322 Albrengues, 2014, LIF mediates proinvasive activation of stromal fibroblasts in cancer, Cell Rep., 7, 1664, 10.1016/j.celrep.2014.04.036 Gaggioli, 2007, Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells, Nat. Cell Biol., 9, 1392, 10.1038/ncb1658 Albrengues, 2015, Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts, Nat. Commun., 6, 10204, 10.1038/ncomms10204 Erez, 2010, Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner, Cancer Cell, 17, 135, 10.1016/j.ccr.2009.12.041 Orimo, 2005, Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion, Cell, 121, 335, 10.1016/j.cell.2005.02.034 Trimboli, 2009, Pten in stromal fibroblasts suppresses mammary epithelial tumours, Nature, 461, 1084, 10.1038/nature08486 Grum-Schwensen, 2005, Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene, Cancer Res., 65, 3772, 10.1158/0008-5472.CAN-04-4510 Malanchi, 2012, Interactions between cancer stem cells and their niche govern metastatic colonization, Nature, 481, 85, 10.1038/nature10694 Wrzesinski, 2007, Transforming growth factor-beta and the immune response: implications for anticancer therapy, Clin. Cancer Res., 13, 5262, 10.1158/1078-0432.CCR-07-1157 Pickup, 2013, The roles of TGFbeta in the tumour microenvironment, Nat. Rev. Cancer, 13, 788, 10.1038/nrc3603 Li, 2008, TGF-beta: a master of all T cell trades, Cell, 134, 392, 10.1016/j.cell.2008.07.025 Murphy, 2002, The lineage decisions of helper T cells, Nat. Rev. Immunol., 2, 933, 10.1038/nri954 Valderrama-Carvajal, 2002, Activin/TGF-beta induce apoptosis through Smad-dependent expression of the lipid phosphatase SHIP, Nat. Cell Biol., 4, 963, 10.1038/ncb885 Chaouchi, 1995, Characterization of transforming growth factor-beta 1 induced apoptosis in normal human B cells and lymphoma B cell lines, Oncogene, 11, 1615 Yamaguchi, 1997, Contrasting effects of TGF-beta 1 and TNF-alpha on the development of dendritic cells from progenitors in mouse bone marrow, Stem Cells, 15, 144, 10.1002/stem.150144 Condamine, 2015, Regulation of tumor metastasis by myeloid-derived suppressor cells, Annu. Rev. Med., 66, 97, 10.1146/annurev-med-051013-052304 Yang, 2008, Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis, Cancer Cell, 13, 23, 10.1016/j.ccr.2007.12.004 Wahl, 1987, Transforming growth factor type beta induces monocyte chemotaxis and growth factor production, Proc. Natl. Acad. Sci. U. S. A., 84, 5788, 10.1073/pnas.84.16.5788 Elgert, 1998, Tumor-induced immune dysfunction: the macrophage connection, J. Leukoc. Biol., 64, 275, 10.1002/jlb.64.3.275 Hao, 2012, Macrophages in tumor microenvironments and the progression of tumors, Clin. Dev. Immunol., 2012, 948098, 10.1155/2012/948098 Joyce, 2009, Microenvironmental regulation of metastasis, Nat. Rev. Cancer, 9, 239, 10.1038/nrc2618 Alleva, 1994, Tumor-induced regulation of suppressor macrophage nitric oxide and TNF-alpha production Role of tumor-derived IL-10, TGF-beta, and prostaglandin E2, J. Immunol., 153, 1674, 10.4049/jimmunol.153.4.1674 Takaki, 2006, TGF-beta1 suppresses IFN-gamma-induced NO production in macrophages by suppressing STAT1 activation and accelerating iNOS protein degradation, Genes Cells, 11, 871, 10.1111/j.1365-2443.2006.00988.x Fridlender, 2009, Polarization of tumor-associated neutrophil phenotype by TGF-beta: N1 versus N2 TAN, Cancer Cell, 16, 183, 10.1016/j.ccr.2009.06.017 Ito, 2006, Tumor-derived TGFbeta-1 induces dendritic cell apoptosis in the sentinel lymph node, J. Immunol., 176, 5637, 10.4049/jimmunol.176.9.5637 Imai, 2012, Inhibition of dendritic cell migration by transforming growth factor-beta1 increases tumor-draining lymph node metastasis, J. Exp. Clin. Cancer Res., 31, 3, 10.1186/1756-9966-31-3 Kobie, 2003, Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines, Cancer Res., 63, 1860 Kiessling, 1975, Natural killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell, Eur. J. Immunol., 5, 117, 10.1002/eji.1830050209 Moretta, 2001, Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis, Annu. Rev. Immunol., 19, 197, 10.1146/annurev.immunol.19.1.197 Castriconi, 2003, Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells, Proc. Natl. Acad. Sci. U. S. A., 100, 4120, 10.1073/pnas.0730640100 Lee, 2004, Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients, J. Immunol., 172, 7335, 10.4049/jimmunol.172.12.7335 Thomas, 2005, TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance, Cancer Cell, 8, 369, 10.1016/j.ccr.2005.10.012 Gorelik, 2001, Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells, Nat. Med., 7, 1118, 10.1038/nm1001-1118 Bottinger, 1997, Biology of TGF-beta in knockout and transgenic mouse models, Kidney Int., 51, 1355, 10.1038/ki.1997.185 Kulkarni, 2002, Function of cytokines within the TGF-beta superfamily as determined from transgenic and gene knockout studies in mice, Curr. Mol. Med., 2, 303, 10.2174/1566524024605699 Letterio, 1996, Transforming growth factor-beta1-deficient mice: identification of isoform-specific activities in vivo, J. Leukoc. Biol., 59, 769, 10.1002/jlb.59.6.769 Letterio, 2005, TGF-beta signaling in T cells: roles in lymphoid and epithelial neoplasia, Oncogene, 24, 5701, 10.1038/sj.onc.1208922 Sakaguchi, 1995, Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases, J. Immunol., 155, 1151, 10.4049/jimmunol.155.3.1151 Oleinika, 2013, Suppression, subversion and escape: the role of regulatory T cells in cancer progression, Clin. Exp. Immunol., 171, 36, 10.1111/j.1365-2249.2012.04657.x Nakamura, 2001, Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta, J. Exp. Med., 194, 629, 10.1084/jem.194.5.629 Fu, 2004, TGF-beta induces Foxp3+T-regulatory cells from CD4+CD25 – precursors, Am. J. Transplant., 4, 1614, 10.1111/j.1600-6143.2004.00566.x Tone, 2008, Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer, Nat. Immunol., 9, 194, 10.1038/ni1549 Shen, 2015, TGF-beta regulates hepatocellular carcinoma progression by inducing Treg cell polarization, Cell. Physiol. Biochem., 35, 1623, 10.1159/000373976 Mangan, 2006, Transforming growth factor-beta induces development of the T(H)17 lineage, Nature, 441, 231, 10.1038/nature04754 Veldhoen, 2006, TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells, Immunity, 24, 179, 10.1016/j.immuni.2006.01.001 Kehrl, 1986, Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth, J. Exp. Med., 163, 1037, 10.1084/jem.163.5.1037 Mehlen, 2006, Metastasis: a question of life or death, Nat. Rev. Cancer, 6, 449, 10.1038/nrc1886 Vanharanta, 2013, Origins of metastatic traits, Cancer Cell, 24, 410, 10.1016/j.ccr.2013.09.007 Ding, 2013, Transforming growth factor beta induces expression of connective tissue growth factor in hepatic progenitor cells through Smad independent signaling, Cell. Signal., 25, 1981, 10.1016/j.cellsig.2013.05.027 Giampieri, 2009, Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility, Nat. Cell Biol., 11, 1287, 10.1038/ncb1973 Eberlein, 2015, E-Cadherin and EpCAM expression by NSCLC tumour cells associate with normal fibroblast activation through a pathway initiated by integrin alphavbeta6 and maintained through TGFbeta signalling, Oncogene, 34, 704, 10.1038/onc.2013.600 Bae, 2016, Chronic TGFbeta stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin beta3-Akt-GSK3beta signaling, Oncotarget, 7, 25366, 10.18632/oncotarget.8295 Yang, 2015, TGF-beta-activated SMAD3/4 complex transcriptionally upregulates N-cadherin expression in non-small cell lung cancer, Lung Cancer, 87, 249, 10.1016/j.lungcan.2014.12.015 Miao, 2013, SPOCK1 is a novel transforming growth factor-beta target gene that regulates lung cancer cell epithelial-mesenchymal transition, Biochem. Biophys. Res. Commun., 440, 792, 10.1016/j.bbrc.2013.10.024 Koeck, 2016, The impact of metformin and salinomycin on transforming growth factor beta-induced epithelial-to-mesenchymal transition in non-small cell lung cancer cell lines, Oncol. Lett., 11, 2946, 10.3892/ol.2016.4323 Izumchenko, 2014, The TGFbeta-miR200-MIG6 pathway orchestrates the EMT-associated kinase switch that induces resistance to EGFR inhibitors, Cancer Res., 74, 3995, 10.1158/0008-5472.CAN-14-0110 Ohshio, 2013, Inhibition of transforming growth factor-beta release from tumor cells reduces their motility associated with epithelial-mesenchymal transition, Oncol. Rep., 30, 1000, 10.3892/or.2013.2505 Risolino, 2014, Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-beta-SMAD3 pathway in non-small cell lung adenocarcinoma, Proc. Natl. Acad. Sci. U. S. A., 111, E3775, 10.1073/pnas.1407074111 Moustakas, 2014, TGFbeta and matrix-regulated epithelial to mesenchymal transition, Biochim. Biophys. Acta, 1840, 2621, 10.1016/j.bbagen.2014.02.004 Sundqvist, 2013, Specific interactions between Smad proteins and AP-1 components determine TGFbeta-induced breast cancer cell invasion, Oncogene, 32, 3606, 10.1038/onc.2012.370 Mise, 2012, Zyxin is a transforming growth factor-beta (TGF-beta)/Smad3 target gene that regulates lung cancer cell motility via integrin alpha5beta1, J. Biol. Chem., 287, 31393, 10.1074/jbc.M112.357624 Salvo, 2014, Combined targeting of TGF-beta1 and integrin beta3 impairs lymph node metastasis in a mouse model of non-small-cell lung cancer, Mol. Cancer, 13, 112, 10.1186/1476-4598-13-112 Parvani, 2015, Silencing beta3 integrin by targeted ECO/siRNA nanoparticles inhibits EMT and metastasis of triple-negative breast cancer, Cancer Res., 75, 2316, 10.1158/0008-5472.CAN-14-3485 Franco, 2010, Snail1 suppresses TGF-beta-induced apoptosis and is sufficient to trigger EMT in hepatocytes, J. Cell Sci., 123, 3467, 10.1242/jcs.068692 Bertran, 2013, Overactivation of the TGF-beta pathway confers a mesenchymal-like phenotype and CXCR4-dependent migratory properties to liver tumor cells, Hepatology, 58, 2032, 10.1002/hep.26597 Fan, 2014, Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma, Cancer Lett., 352, 160, 10.1016/j.canlet.2014.05.008 Pu, 2014, PARP-1 regulates epithelial-mesenchymal transition (EMT) in prostate tumorigenesis, Carcinogenesis, 35, 2592, 10.1093/carcin/bgu183 Thakur, 2014, TGFbeta-induced invasion of prostate cancer cells is promoted by c-Jun-dependent transcriptional activation of Snail1, Cell Cycle, 13, 2400, 10.4161/cc.29339 Shiota, 2012, Clusterin mediates TGF-beta-induced epithelial-mesenchymal transition and metastasis via Twist1 in prostate cancer cells, Cancer Res., 72, 5261, 10.1158/0008-5472.CAN-12-0254 Morimoto, 2014, NEDD9 crucially regulates TGF-beta-triggered epithelial-mesenchymal transition and cell invasion in prostate cancer cells: involvement in cancer progressiveness, Prostate, 74, 901, 10.1002/pros.22809 Coniglio, 2013, Review: molecular mechanism of microglia stimulated glioblastoma invasion, Matrix Biol., 32, 372, 10.1016/j.matbio.2013.07.008 Nana, 2015, Overview of transforming growth factor beta superfamily involvement in glioblastoma initiation and progression, Asian Pac. J. Cancer Prev.: APJCP, 16, 6813, 10.7314/APJCP.2015.16.16.6813 Lee, 2014, Targeting the epithelial to mesenchymal transition in glioblastoma: the emerging role of MET signaling, OncoTargets Ther., 7, 1933 Joseph, 2014, TGF-beta is an inducer of ZEB1-dependent mesenchymal transdifferentiation in glioblastoma that is associated with tumor invasion, Cell Death Dis., 5, e1443, 10.1038/cddis.2014.395 Mahabir, 2014, Sustained elevation of Snail promotes glial-mesenchymal transition after irradiation in malignant glioma, Neuro Oncol., 16, 671, 10.1093/neuonc/not239 Penuelas, 2009, TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma, Cancer Cell, 15, 315, 10.1016/j.ccr.2009.02.011 Cosset, 2012, Involvement of the TGFbeta pathway in the regulation of alpha5 beta1 integrins by caveolin-1 in human glioblastoma, Int. J. Cancer, 131, 601, 10.1002/ijc.26415 Roth, 2013, Integrin control of the transforming growth factor-beta pathway in glioblastoma, Brain, 136, 564, 10.1093/brain/aws351 Friedl, 2004, Prespecification and plasticity: shifting mechanisms of cell migration, Curr. Opin. Cell Biol., 16, 14, 10.1016/j.ceb.2003.11.001 Sanz-Moreno, 2008, Rac activation and inactivation control plasticity of tumor cell movement, Cell, 135, 510, 10.1016/j.cell.2008.09.043 Cantelli, 2015, TGF-beta-induced transcription sustains amoeboid melanoma migration and dissemination, Curr. Biol.: CB, 25, 2899, 10.1016/j.cub.2015.09.054 Mihira, 2012, TGF-beta-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A, J. Biochem., 151, 145, 10.1093/jb/mvr121 Sanz-Moreno, 2011, ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma, Cancer Cell, 20, 229, 10.1016/j.ccr.2011.06.018 Lauden, 2014, TGF-beta-induced (TGFBI) protein in melanoma: a signature of high metastatic potential, J. Invest. Dermatol., 134, 1675, 10.1038/jid.2014.20 Tulley, 2014, Transcriptional regulation of seprase in invasive melanoma cells by transforming growth factor-beta signaling, J. Biol. Chem., 289, 15280, 10.1074/jbc.M114.568501 Yin, 2012, TGF-beta signaling, activated stromal fibroblasts, and cysteine cathepsins B and L drive the invasive growth of human melanoma cells, Am. J. Pathol., 181, 2202, 10.1016/j.ajpath.2012.08.027 Wardwell-Ozgo, 2014, HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome, Oncogene, 33, 1017, 10.1038/onc.2013.30 Alexaki, 2010, GLI2-mediated melanoma invasion and metastasis, J. Natl. Cancer Inst., 102, 1148, 10.1093/jnci/djq257 DiVito, 2014, Id2, Id3 and Id4 overcome a Smad7-mediated block in tumorigenesis, generating TGF-beta-independent melanoma, Carcinogenesis, 35, 951, 10.1093/carcin/bgt479 Rintoul, 2002, Extracellular matrix regulation of drug resistance in small-cell lung cancer, Clin. Sci. (Lond.), 102, 417, 10.1042/cs1020417 Wyckoff, 2000, A critical step in metastasis: in vivo analysis of intravasation at the primary tumor, Cancer Res., 60, 2504 Reymond, 2013, Crossing the endothelial barrier during metastasis, Nat. Rev. Cancer, 13, 858, 10.1038/nrc3628 Pang, 2016, TGF-beta1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis, Oncogene, 35, 748, 10.1038/onc.2015.133 Yu, 2015, TGF-beta/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis, Genes Dev., 29, 250, 10.1101/gad.248963.114 Krizbai, 2015, Endothelial-mesenchymal transition of brain endothelial cells: possible role during metastatic extravasation, PLoS One, 10, e0123845, 10.1371/journal.pone.0119655 Feng, 2013, Beta3 integrin promotes TGF-beta1/H2O2/HOCl-mediated induction of metastatic phenotype of hepatocellular carcinoma cells by enhancing TGF-beta1 signaling, PLoS One, 8, e79857, 10.1371/journal.pone.0079857 Vazquez, 2013, TGF-beta specifically enhances the metastatic attributes of murine lung adenocarcinoma: implications for human non-small cell lung cancer, Clin. Exp. Metastasis, 30, 993, 10.1007/s10585-013-9598-1 Jiang, 2015, Metabolic reprogramming during TGFbeta1-induced epithelial-to-mesenchymal transition, Oncogene, 34, 3908, 10.1038/onc.2014.321 Morishita, 2013, HMGA2 is a driver of tumor metastasis, Cancer Res., 73, 4289, 10.1158/0008-5472.CAN-12-3848 Huang, 2012, MED12 controls the response to multiple cancer drugs through regulation of TGF-beta receptor signaling, Cell, 151, 937, 10.1016/j.cell.2012.10.035 Simic, 2013, SIRT1 suppresses the epithelial-to-mesenchymal transition in cancer metastasis and organ fibrosis, Cell Rep., 3, 1175, 10.1016/j.celrep.2013.03.019 Chen, 2013, DEAR1 is a chromosome 1p35 tumor suppressor and master regulator of TGF-beta-driven epithelial-mesenchymal transition, Cancer Discov., 3, 1172, 10.1158/2159-8290.CD-12-0499 Yuan, 2014, A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma, Cancer Cell, 25, 666, 10.1016/j.ccr.2014.03.010 Shi, 2015, LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer, Oncotarget, 6, 11652, 10.18632/oncotarget.3457 Richards, 2015, Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) beta: LncRNA-hit-mediated TGFbeta-induced epithelial to mesenchymal transition in mammary epithelia, J. Biol. Chem., 290, 6857, 10.1074/jbc.M114.610915 Wong, 2014, Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma, Hepatology, 60, 1645, 10.1002/hep.27320 Mishra, 2011, Blockade of transforming growth factor-beta (TGFbeta) signaling inhibits osteoblastic tumorigenesis by a novel human prostate cancer cell line, Prostate, 71, 1441, 10.1002/pros.21361 Siu, 2015, Transforming growth factor-beta promotes prostate bone metastasis through induction of microRNA-96 and activation of the mTOR pathway, Oncogene, 34, 4767, 10.1038/onc.2014.414 Hansen, 2014, ALCAM/CD166 is a TGF-beta-responsive marker and functional regulator of prostate cancer metastasis to bone, Cancer Res., 74, 1404, 10.1158/0008-5472.CAN-13-1296 Leblanc, 2016, Metastasis: new functional implications of platelets and megakaryocytes, Blood, 128, 24, 10.1182/blood-2016-01-636399 Wang, 2015, EWI-2 negatively regulates TGF-beta signaling leading to altered melanoma growth and metastasis, Cell Res., 25, 370, 10.1038/cr.2015.17 Fakhrai, 2006, Phase I clinical trial of a TGF-beta antisense-modified tumor cell vaccine in patients with advanced glioma, Cancer Gene Ther., 13, 1052, 10.1038/sj.cgt.7700975 Melisi, 2008, LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis, Mol. Cancer Ther., 7, 829, 10.1158/1535-7163.MCT-07-0337 Nemunaitis, 2006, Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer, J. Clin. Oncol., 24, 4721, 10.1200/JCO.2005.05.5335 Giannelli, 2016, The rationale for targeting TGF-beta in chronic liver diseases, Eur. J. Clin. Invest., 46, 349, 10.1111/eci.12596 Giaccone, 2015, A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer, Eur. J. Cancer, 51, 2321, 10.1016/j.ejca.2015.07.035 Morris, 2014, Phase I study of GC1008 (fresolimumab): a human anti-transforming growth factor-beta (TGFbeta) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma, PLoS One, 9, e90353, 10.1371/journal.pone.0090353