Review

The potential role of transforming growth factor beta family ligand interactions in prostate cancer

  • Received: 19 October 2016 Accepted: 25 January 2017 Published: 13 February 2017
  • The transforming growth factor beta (TGF-β) family plays an important role in embryonic development and control of the cell cycle. Members of the TGF-β family have pleiotropic functions and are involved in both the inhibition and progression of various cancers. In particular, deregulation of the TGF-β family has been associated with prostate cancer, as both a mechanism of disease progression and a possible therapeutic target. This review concentrates on the TGF-βs, activins and inhibins, bone morphogenetic proteins and NODAL and their connection to prostate cancer. Whilst most studies examine the family members in isolation, there are multiple interactions that may occur between members which can alter their function. Such interactions include ligand competition for receptor binding and shared intracellular pathways such as the Mothers against decapentaplegic (SMAD) proteins. Another mechanism for interaction within the TGF-β family is facilitated by their dimeric structure; heterodimers can form which exhibit different functional capabilities to their homodimeric counterparts. The potential formation of TGF-β family heterodimers has not been well examined in prostate cancer. The multiple methods of interrelations between members highlights the need for gross analysis of the TGF-β family and related factors in association with prostate cancer, in order to discover possible future avenues for TGF-β based diagnosis and treatments of the disease. This review describes the role of the TGF-β family of proteins in cancer and, in particular, prostate cancer. After a brief overview, the role of individual members of the family is considered and how these members may be involved in prostate cancer growth is discussed. The review highlights the complex interactions that occur between family members and that may contribute to the progression of prostate cancer.

    Citation: Kit P. Croxford, Karen L. Reader, Helen D. Nicholson. The potential role of transforming growth factor beta family ligand interactions in prostate cancer[J]. AIMS Molecular Science, 2017, 4(1): 41-61. doi: 10.3934/molsci.2017.1.41

    Related Papers:

  • The transforming growth factor beta (TGF-β) family plays an important role in embryonic development and control of the cell cycle. Members of the TGF-β family have pleiotropic functions and are involved in both the inhibition and progression of various cancers. In particular, deregulation of the TGF-β family has been associated with prostate cancer, as both a mechanism of disease progression and a possible therapeutic target. This review concentrates on the TGF-βs, activins and inhibins, bone morphogenetic proteins and NODAL and their connection to prostate cancer. Whilst most studies examine the family members in isolation, there are multiple interactions that may occur between members which can alter their function. Such interactions include ligand competition for receptor binding and shared intracellular pathways such as the Mothers against decapentaplegic (SMAD) proteins. Another mechanism for interaction within the TGF-β family is facilitated by their dimeric structure; heterodimers can form which exhibit different functional capabilities to their homodimeric counterparts. The potential formation of TGF-β family heterodimers has not been well examined in prostate cancer. The multiple methods of interrelations between members highlights the need for gross analysis of the TGF-β family and related factors in association with prostate cancer, in order to discover possible future avenues for TGF-β based diagnosis and treatments of the disease. This review describes the role of the TGF-β family of proteins in cancer and, in particular, prostate cancer. After a brief overview, the role of individual members of the family is considered and how these members may be involved in prostate cancer growth is discussed. The review highlights the complex interactions that occur between family members and that may contribute to the progression of prostate cancer.


    加载中
    [1] da Silva HB, Amaral EP, Nolasco EL, et al. (2013) Dissecting major signaling pathways throughout the development of prostate cancer. Prostate Cancer 2013: 920612.
    [2] Chang H, Brown CW, Matzuk MM (2002) Genetic analysis of the mammalian transforming growth factor-β superfamily. Endocr Rev 23: 787-823. doi: 10.1210/er.2002-0003
    [3] Massagué J (2008) TGFβ in cancer. Cell 134: 215-230. doi: 10.1016/j.cell.2008.07.001
    [4] Zhang YE (2009) Non-Smad pathways in TGF-β signaling. Cell Res 19: 128-139. doi: 10.1038/cr.2008.328
    [5] Heldin C-H, Moustakas A (2016) Signaling Receptors for TGF-β Family Members. Cold Spring Harb Perspect Biol 8: a022053. doi: 10.1101/cshperspect.a022053
    [6] Morikawa M, Derynck R, Miyazono K (2016) TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harb Perspect Biol 8: a021873. doi: 10.1101/cshperspect.a021873
    [7] Jenkins G (2008) The role of proteases in transforming growth factor-beta activation. Int J Biochem Cell Biol 40: 1068-1078. doi: 10.1016/j.biocel.2007.11.026
    [8] Johnson KE, Makanji Y, Temple-Smith P, et al. (2016) Biological activity and in vivo half-life of pro-activin A in male rats. Mol Cell Endocrinol 422: 84-92. doi: 10.1016/j.mce.2015.12.007
    [9] Walton KL, Kelly EK, Chan KL, et al. (2015) Inhibin biosynthesis and activity are limited by a prodomain-derived peptide. Endocrinology 156: 3047-3057. doi: 10.1210/en.2014-2005
    [10] Walton KL, Makanji Y, Harrison CA (2012) New insights into the mechanisms of activin action and inhibition. Mol Cell Endocrinol 359: 2-12. doi: 10.1016/j.mce.2011.06.030
    [11] De Caestecker M (2004) The transforming growth factor-β superfamily of receptors. Cytokine Growth Factor Rev 15: 1-11. doi: 10.1016/j.cytogfr.2003.10.004
    [12] Brodin G, ten Dijke P, Funa K, et al. (1999) Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration. Cancer Res 59: 2731-2738.
    [13] Shi Y, Massagué J (2003) Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113: 685-700. doi: 10.1016/S0092-8674(03)00432-X
    [14] Sun PD, Davies DR (1995) The cystine-knot growth-factor superfamily. Annu Rev Biophys Biomol Struct 24: 269-291. doi: 10.1146/annurev.bb.24.060195.001413
    [15] Lebrun J-J (2012) The dual role of TGF in human cancer: from tumor suppression to cancer metastasis. ISRN Mol Biol 2012.
    [16] Bierie B, Moses HL (2006) Tumour microenvironment: TGFβ: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 6: 506-520. doi: 10.1038/nrc1926
    [17] Xie L, Law BK, Chytil AM, et al. (2004) Activation of the Erk pathway is required for TGF-β1-induced EMT in vitro. Neoplasia 6: 603-610. doi: 10.1593/neo.04241
    [18] Beck C, Schreiber H, Rowley DA (2001) Role of TGF-β in immune-evasion of cancer. Microsc Res Tech 52: 387-395.
    [19] Margheri F, Schiavone N, Papucci L, et al. (2012) GDF5 regulates TGFß-dependent angiogenesis in breast carcinoma MCF-7 cells: in vitro and in vivo control by anti-TGFß peptides. PLoS One 7: e50342. doi: 10.1371/journal.pone.0050342
    [20] Futakuchi M, Nannuru KC, Varney ML, et al. (2009) Transforming growth factor-β signaling at the tumor-bone interface promotes mammary tumor growth and osteoclast activation. Cancer Sci 100: 71-81. doi: 10.1111/j.1349-7006.2008.01012.x
    [21] Sugatani T, Alvarez U, Hruska K (2003) Activin A stimulates IκB‐α/NFκB and rank expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors. J Cell Biochem 90: 59-67. doi: 10.1002/jcb.10613
    [22] Gupta DK, Singh N, Sahu DK (2014) TGF-β Mediated Crosstalk Between Malignant Hepatocyte and Tumor Microenvironment in Hepatocellular Carcinoma. Cancer Growth Metastasis 7: 1.
    [23] Marino FE, Risbridger G, Gold E (2013) The therapeutic potential of blocking the activin signalling pathway. Cytokine Growth Factor Rev 24: 477-484. doi: 10.1016/j.cytogfr.2013.04.006
    [24] Siegel PM, Massagué J (2003) Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nat Rev Cancer 3: 807-820. doi: 10.1038/nrc1208
    [25] Irigoyen J, Munoz-Canoves P, Montero L, et al. (1999) The plasminogen activator system: biology and regulation. Cell Mol Life Sci 56: 104-132. doi: 10.1007/PL00000615
    [26] Li WY, Chong SS, Huang EY, et al. (2003) Plasminogen activator/plasmin system: a major player in wound healing? Wound Repair Regen 11: 239-247. doi: 10.1046/j.1524-475X.2003.11402.x
    [27] Pulukuri SM, Gondi CS, Lakka SS, et al. (2005) RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity in vivo. J Biol Chem 280: 36529-36540. doi: 10.1074/jbc.M503111200
    [28] Hartwell KA, Muir B, Reinhardt F, et al. (2006) The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc Natl Acad Sci U S A 103: 18969-18974. doi: 10.1073/pnas.0608636103
    [29] Padua D, Massagué J (2009) Roles of TGFβ in metastasis. Cell Res 19: 89-102. doi: 10.1038/cr.2008.316
    [30] Mundy GR (2002) Metastasis: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2: 584-593. doi: 10.1038/nrc867
    [31] Logothetis CJ, Lin S-H (2005) Osteoblasts in prostate cancer metastasis to bone. Nat Rev Cancer 5: 21-28. doi: 10.1038/nrc1528
    [32] Chen G, Deng C, Li Y-P (2012) TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 8: 272-288. doi: 10.7150/ijbs.2929
    [33] Tsuchida K, Nakatani M, Hitachi K, et al. (2009) Activin signaling as an emerging target for therapeutic interventions. Cell Commun Signal 7: 10.1186. doi: 10.1186/1478-811X-7-10
    [34] Buijs J, Van Der Horst G, Van Den Hoogen C, et al. (2012) The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation. Oncogene 31: 2164-2174. doi: 10.1038/onc.2011.400
    [35] Schnepp B, Hua X (2003) A Tumor Suppressing Duo: TGFβ and Activin Modulate a Similar Transcriptome. Cancer Biol Ther 2: 171-172. doi: 10.4161/cbt.2.2.334
    [36] Mittl PR, Priestle JP, Cox DA, et al. (1996) The crystal structure of TGF‐β3 and comparison to TGF‐β2: implications for receptor binding. Protein Science 5: 1261-1271. doi: 10.1002/pro.5560050705
    [37] Gatherer D, Ten Dijke P, Baird DT, et al. (1990) Expression of TGF-isoforms during first trimester human embryogenesis. Development 110: 445-460.
    [38] Millan FA, Denhez F, Kondaiah P, et al. (1991) Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo. Development 111: 131-143.
    [39] Pelton RW, Saxena B, Jones M, et al. (1991) Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J Cell Biol 115: 1091-1105. doi: 10.1083/jcb.115.4.1091
    [40] López-Casillas F, Wrana JL, Massagué J (1993) Betaglycan presents ligand to the TGFβ signaling receptor. Cell 73: 1435-1444. doi: 10.1016/0092-8674(93)90368-Z
    [41] Piek E, Heldin C-H, Ten Dijke P (1999) Specificity, diversity, and regulation in TGF-β superfamily signaling. FASEB J 13: 2105-2124.
    [42] David D, Nair SA, Pillai MR (2013) Smurf E3 ubiquitin ligases at the cross roads of oncogenesis and tumor suppression. Biochim Biophys Acta 1835: 119-128.
    [43] Robertson IB, Horiguchi M, Zilberberg L, et al. (2015) Latent TGF-β-binding proteins. Matrix Biology 47: 44-53. doi: 10.1016/j.matbio.2015.05.005
    [44] Butz H, Rácz K, Hunyady L, et al. (2012) Crosstalk between TGF-β signaling and the microRNA machinery. Trends Pharmacol Sci 33: 382-393. doi: 10.1016/j.tips.2012.04.003
    [45] Zhong H, Wang H-R, Yang S, et al. (2010) Targeting Smad4 links microRNA-146a to the TGF-β pathway during retinoid acid induction in acute promyelocytic leukemia cell line. Int J Hematol 92: 129-135. doi: 10.1007/s12185-010-0626-5
    [46] Ottley E, Gold E (2014) microRNA and non-canonical TGF-β signalling: Implications for prostate cancer therapy. Crit Rev Oncol Hematol 92: 49-60. doi: 10.1016/j.critrevonc.2014.05.011
    [47] van den Bosch MH, Blom AB, van Lent PL, et al. (2014) Canonical Wnt signaling skews TGF-β signaling in chondrocytes towards signaling via ALK1 and Smad 1/5/8. Cell Signal 26: 951-958. doi: 10.1016/j.cellsig.2014.01.021
    [48] Grönroos E, Kingston IJ, Ramachandran A, et al. (2012) Transforming growth factor β inhibits bone morphogenetic protein-induced transcription through novel phosphorylated Smad1/5-Smad3 complexes. Mol Cell Biol 32: 2904-2916. doi: 10.1128/MCB.00231-12
    [49] Liu IM, Schilling SH, Knouse KA, et al. (2009) TGFβ‐stimulated Smad1/5 phosphorylation requires the ALK5 L45 loop and mediates the pro‐migratory TGFβ switch. EMBO J 28: 88-98. doi: 10.1038/emboj.2008.266
    [50] Perry KT, Anthony CT, Steiner MS (1997) Immunohistochemical localization of TGFβ1, TGFβ2, and TGFβ3 in normal and malignant human prostate. Prostate 33: 133-140.
    [51] Danielpour D (2005) Functions and regulation of transforming growth factor-beta (TGF-beta) in the prostate. Eur J Cancer 41: 846-857. doi: 10.1016/j.ejca.2004.12.027
    [52] Dallas SL, Zhao S, Cramer SD, et al. (2005) Preferential production of latent transforming growth factor beta-2 by primary prostatic epithelial cells and its activation by prostate-specific antigen. J Cell Physiol 202: 361-370. doi: 10.1002/jcp.20147
    [53] Laverty H, Wakefield L, Occleston N, et al. (2009) TGF-β3 and cancer: a review. Cytokine Growth Factor Rev 20: 305-317. doi: 10.1016/j.cytogfr.2009.07.002
    [54] Parada D, Arciniegas E, Moreira O, et al. (2003) Transforming growth factor-beta2 and beta3 expression in carcinoma of the prostate. Arch Esp Urol 57: 93-99.
    [55] Djonov V, Ball RK, Graf S, et al. (1997) Transforming growth factor‐β3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma. Prostate 31: 103-109.
    [56] Hisataki T, Itoh N, Suzuki K, et al. (2004) Modulation of phenotype of human prostatic stromal cells by transforming growth factor‐betas. Prostate 58: 174-182. doi: 10.1002/pros.10320
    [57] Ao M, Williams K, Bhowmick NA, et al. (2006) Transforming growth factor-β promotes invasion in tumorigenic but not in nontumorigenic human prostatic epithelial cells. Cancer Res 66: 8007-8016. doi: 10.1158/0008-5472.CAN-05-4451
    [58] Wikström P, Stattin P, Franck‐Lissbrant I, et al. (1998) Transforming growth factor β1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer. Prostate 37: 19-29.
    [59] Steiner MS, Barrack ER (1992) Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. Mol Endocrinol 6: 15-25.
    [60] Steiner MS, Zhou Z-Z, Tonb DC, et al. (1994) Expression of transforming growth factor-beta 1 in prostate cancer. Endocrinology 135: 2240-2247.
    [61] Mu Y, Sundar R, Thakur N, et al. (2011) TRAF6 ubiquitinates TGF [beta] type I receptor to promote its cleavage and nuclear translocation in cancer. Nat Commun 2: 330. doi: 10.1038/ncomms1332
    [62] Wan Y, Yang M, Kolattukudy S, et al. (2010) Activation of cAMP-responsive-element-binding protein by PI3 kinase and p38 MAPK is essential for elevated expression of transforming growth factor β2 in cancer cells. J Interferon Cytokine Res 30: 677-681. doi: 10.1089/jir.2009.0117
    [63] Bang Y-J, Kim S-J, Danielpour D, et al. (1992) Cyclic AMP induces transforming growth factor beta 2 gene expression and growth arrest in the human androgen-independent prostate carcinoma cell line PC-3. Proc Natl Acad Sci U S A 89: 3556-3560. doi: 10.1073/pnas.89.8.3556
    [64] Cho HJ, Baek KE, Saika S, et al. (2007) Snail is required for transforming growth factor-β-induced epithelial–mesenchymal transition by activating PI3 kinase/Akt signal pathway. Biochem Biophys Res Commun 353: 337-343. doi: 10.1016/j.bbrc.2006.12.035
    [65] Walker L, Millena AC, Strong N, et al. (2013) Expression of TGFβ3 and its effects on migratory and invasive behavior of prostate cancer cells: involvement of PI3-kinase/AKT signaling pathway. Clin Exp Metastasis 30: 13-23. doi: 10.1007/s10585-012-9494-0
    [66] Vo BT, Morton Jr D, Komaragiri S, et al. (2013) TGF-β effects on prostate cancer cell migration and invasion are mediated by PGE2 through activation of PI3K/AKT/mTOR pathway. Endocrinology 154: 1768-1779. doi: 10.1210/en.2012-2074
    [67] Williams RH, Stapleton A, Yang G, et al. (1996) Reduced levels of transforming growth factor beta receptor type II in human prostate cancer: an immunohistochemical study. Clin Cancer Res 2: 635-640.
    [68] Demagny H, De Robertis EM (2015) Smad4/DPC4: A barrier against tumor progression driven by RTK/Ras/Erk and Wnt/GSK3 signaling. Mol Cell Oncol: e989133.
    [69] Hahn SA, Schutte M, Hoque AS, et al. (1996) DPC4, a candidate tumor suppressor gene at human chromosome 18q21. 1. Science 271: 350-353. doi: 10.1126/science.271.5247.350
    [70] Papageorgis P (2015) TGFbeta Signaling in Tumor Initiation, Epithelial-to-Mesenchymal Transition, and Metastasis. J Oncol 2015: 587193.
    [71] Hofmann TG, Stollberg N, Schmitz ML, et al. (2003) HIPK2 regulates transforming growth factor-β-induced c-Jun NH2-terminal kinase activation and apoptosis in human hepatoma cells. Cancer Res 63: 8271-8277.
    [72] Edlund S, Bu S, Schuster N, et al. (2003) Transforming Growth Factor-β1 (TGF-β)–induced Apoptosis of Prostate Cancer Cells Involves Smad7-dependent Activation of p38 by TGF-β-activated Kinase 1 and Mitogen-activated Protein Kinase Kinase 3. Mol Biol Cell 14: 529-544. doi: 10.1091/mbc.02-03-0037
    [73] Kang H-Y, Huang K-E, Chang SY, et al. (2002) Differential modulation of androgen receptor-mediated transactivation by Smad3 and tumor suppressor Smad4. J Biol Chem 277: 43749-43756. doi: 10.1074/jbc.M205603200
    [74] Micke P (2004) Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer 45: S163-S175. doi: 10.1016/j.lungcan.2004.07.977
    [75] Sheng J, Chen W, Zhu HJ (2015) The immune suppressive function of transforming growth factor-beta (TGF-beta) in human diseases. Growth Factors 33: 92-101. doi: 10.3109/08977194.2015.1010645
    [76] Mu Y, Gudey SK, Landström M (2012) Non-Smad signaling pathways. Cell Tissue Res 347: 11-20. doi: 10.1007/s00441-011-1201-y
    [77] Thompson TB, Cook RW, Chapman SC, et al. (2004) Beta A versus beta B: is it merely a matter of expression? Mol Cell Endocrinol 225: 9-17. doi: 10.1016/j.mce.2004.02.007
    [78] Ryu B, Kern SE (2003) The essential similarity of TGFβ and activin receptor transcriptional responses in cancer cells. Cancer Biol Ther 2: 164-170. doi: 10.4161/cbt.2.2.276
    [79] Loomans HA, Andl CD (2014) Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion. Cancers 7: 70-91. doi: 10.3390/cancers7010070
    [80] Gold E, Marino FE, Harrison C, et al. (2013) Activin‐βc reduces reproductive tumour progression and abolishes cancer‐associated cachexia in inhibin‐deficient mice. J Pathol 229: 599-607. doi: 10.1002/path.4142
    [81] Marino FE, Risbridger G, Gold E (2014) The inhibin/activin signalling pathway in human gonadal and adrenal cancers. Mol Hum Reprod 20: 1223-1237. doi: 10.1093/molehr/gau074
    [82] Mellor SL, Cranfield M, Ries R, et al. (2000) Localization of Activin βA-, β B-, andβ C-Subunits in Human Prostate and Evidence for Formation of New Activin Heterodimers ofβ C-Subunit 1. J Clin Endocrinol Metab 85: 4851-4858.
    [83] Mellor SL, Ball EM, O'Connor AE, et al. (2003) Activin βC-subunit heterodimers provide a new mechanism of regulating activin levels in the prostate. Endocrinology 144: 4410-4419. doi: 10.1210/en.2003-0225
    [84] Stenvers KL, Findlay JK (2010) Inhibins: from reproductive hormones to tumor suppressors. Trends Endocrinol Metab 21: 174-180. doi: 10.1016/j.tem.2009.11.009
    [85] Walton KL, Makanji Y, Wilce MC, et al. (2009) A common biosynthetic pathway governs the dimerization and secretion of inhibin and related transforming growth factor β (TGFβ) ligands. J Biol Chem 284: 9311-9320. doi: 10.1074/jbc.M808763200
    [86] Johnson KE, Makanji Y, Temple-Smith P, et al. (2016) Biological activity and in vivo half-life of pro-activin A in male rats. Mol Cell Endocrinol 422: 84-92. doi: 10.1016/j.mce.2015.12.007
    [87] Sheth A, Panse G, Vaze A, et al. (1981) Inhibin in the human prostate. Arch Androl 6: 317-321. doi: 10.3109/01485018108987543
    [88] Sathe VS, Sheth NA, Phadke MA, et al. (1987) Biosynthesis and localization of inhibin in human prostate. Prostate 10: 33-43. doi: 10.1002/pros.2990100107
    [89] Thomas TZ, Wang H, Niclasen P, et al. (1997) Expression and localization of activin subunits and follistatins in tissues from men with high grade prostate cancer. J Clin Endocrinol Metab 82: 3851-3858. doi: 10.1210/jcem.82.11.4374
    [90] Balanathan P, Ball EM, Wang H, et al. (2004) Epigenetic regulation of inhibin alpha-subunit gene in prostate cancer cell lines. J Mol Endocrinol 32: 55-67. doi: 10.1677/jme.0.0320055
    [91] Mellor SL, Richards MG, Pedersen JS, et al. (1998) Loss of the Expression and Localization of Inhibinα-Subunit in High Grade Prostate Cancer 1. J Clin Endocrinol Metab 83: 969-975.
    [92] Risbridger G, Shibata A, Ferguson K, et al. (2004) Elevated expression of inhibin α in prostate cancer. J Urol 171: 192-196. doi: 10.1097/01.ju.0000100048.98807.b7
    [93] Matzuk M, Finegold M, Mather J, et al. (1994) Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice. Proc Natl Acad Sci U S A 91: 8817-8821. doi: 10.1073/pnas.91.19.8817
    [94] Coerver KA, Woodruff TK, Finegold MJ, et al. (1996) Activin signaling through activin receptor type II causes the cachexia-like symptoms in inhibin-deficient mice. Mol Endocrinol 10: 534-543.
    [95] Dalkin A, Gilrain J, Bradshaw D, et al. (1996) Activin inhibition of prostate cancer cell growth: selective actions on androgen-responsive LNCaP cells. Endocrinology 137: 5230-5235.
    [96] Liu QY, Niranjan B, Gomes P, et al. (1996) Inhibitory effects of activin on the growth and morphogenesis of primary and transformed mammary epithelial cells. Cancer Res 56: 1155-1163.
    [97] Valderrama-Carvajal H, Cocolakis E, Lacerte A, et al. (2002) Activin/TGF-β induce apoptosis through Smad-dependent expression of the lipid phosphatase SHIP. Nat Cell Biol 4: 963-969. doi: 10.1038/ncb885
    [98] Leto G, Incorvaia L, Badalamenti G, et al. (2006) Activin A circulating levels in patients with bone metastasis from breast or prostate cancer. Clin Exp Metastasis 23: 117-122. doi: 10.1007/s10585-006-9010-5
    [99] Sottnik JL, Keller ET (2013) Understanding and targeting osteoclastic activity in prostate cancer bone metastases. Curr Mol Med 13: 626-639. doi: 10.2174/1566524011313040012
    [100] Gold E, Jetly N, O'Bryan MK, et al. (2009) Activin C antagonizes activin A in vitro and overexpression leads to pathologies in vivo. Am J Pathol 174: 184-195. doi: 10.2353/ajpath.2009.080296
    [101] Wakefield LM, Hill CS (2013) Beyond TGFβ: roles of other TGFβ superfamily members in cancer. Nat Rev Cancer 13: 328-341. doi: 10.1038/nrc3500
    [102] Katagiri T, Watabe T (2016) Bone Morphogenetic Proteins. Cold Spring Harb Perspect Biol 8: a021899. doi: 10.1101/cshperspect.a021899
    [103] Wozney JM, Rosen V, Celeste AJ, et al. (1988) Novel regulators of bone formation: molecular clones and activities. Science 242: 1528-1534. doi: 10.1126/science.3201241
    [104] Balboni AL, Cherukuri P, Ung M, et al. (2015) p53 and ΔNp63α Coregulate the Transcriptional and Cellular Response to TGFβ and BMP Signals. Mol Cancer Res 13: 732-742. doi: 10.1158/1541-7786.MCR-14-0152-T
    [105] Herpin A, Lelong C, Favrel P (2004) Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans. Dev Comp Immunol 28: 461-485. doi: 10.1016/j.dci.2003.09.007
    [106] Pils D, Wittinger M, Petz M, et al. (2010) BAMBI is overexpressed in ovarian cancer and co-translocates with Smads into the nucleus upon TGF-ß treatment. Gynecol Oncol 117: 189-197. doi: 10.1016/j.ygyno.2009.12.034
    [107] Cao X, Chen D (2005) The BMP signaling and in vivo bone formation. Gene 357: 1-8. doi: 10.1016/j.gene.2005.06.017
    [108] Onichtchouk D, Chen Y-G, Dosch R, et al. (1999) Silencing of TGF-β signalling by the pseudoreceptor BAMBI. Nature 401: 480-485. doi: 10.1038/46794
    [109] Gamer LW, Cox K, Carlo JM, et al. (2009) Overexpression of BMP3 in the developing skeleton alters endochondral bone formation resulting in spontaneous rib fractures. Dev Dynam 238: 2374-2381. doi: 10.1002/dvdy.22048
    [110] Gamer LW, Nove J, Levin M, et al. (2005) BMP-3 is a novel inhibitor of both activin and BMP-4 signaling in Xenopus embryos. Dev Biol 285: 156-168. doi: 10.1016/j.ydbio.2005.06.012
    [111] Stewart A, Guan H, Yang K (2010) BMP‐3 promotes mesenchymal stem cell proliferation through the TGF‐β/activin signaling pathway. J Cell Physiol 223: 658-666.
    [112] Olsen OE, Wader KF, Hella H, et al. (2015) Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B. Cell Commun Signal 13: 27. doi: 10.1186/s12964-015-0104-z
    [113] Harris SE, Harris MA, Mahy P, et al. (1994) Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells. Prostate 24: 204-211. doi: 10.1002/pros.2990240406
    [114] Masuda H, Fukabori Y, Nakano K, et al. (2004) Expression of bone morphogenetic protein‐7 (BMP‐7) in human prostate. Prostate 59: 101-106. doi: 10.1002/pros.20030
    [115] Lamm ML, Podlasek CA, Barnett DH, et al. (2001) Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Dev Biol 232: 301-314. doi: 10.1006/dbio.2001.0187
    [116] Ye L, Lewis-Russell JM, Kyanaston HG, et al. (2007) Bone morphogenetic proteins and their receptor signaling in prostate cancer. Histol Histopathol 22: 1129-1147.
    [117] Dai J, Keller J, Zhang J, et al. (2005) Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res 65: 8274-8285. doi: 10.1158/0008-5472.CAN-05-1891
    [118] Liao A, Wang W, Sun D, et al. (2014) Bone morphogenetic protein 2 mediates epithelial-mesenchymal transition via AKT and ERK signaling pathways in gastric cancer. Tumour Biol: 1-6.
    [119] Lai TH, Fong YC, Fu WM, et al. (2008) Osteoblasts‐derived BMP‐2 enhances the motility of prostate cancer cells via activation of integrins. Prostate 68: 1341-1353. doi: 10.1002/pros.20799
    [120] Feeley BT, Krenek L, Liu N, et al. (2006) Overexpression of noggin inhibits BMP-mediated growth of osteolytic prostate cancer lesions. Bone 38: 154-166. doi: 10.1016/j.bone.2005.07.015
    [121] Kwon SJ, Lee GT, Lee JH, et al. (2014) Mechanism of pro‐tumorigenic effect of BMP‐6: Neovascularization involving tumor‐associated macrophages and IL‐1α. Prostate 74: 121-133. doi: 10.1002/pros.22734
    [122] Piccirillo S, Reynolds B, Zanetti N, et al. (2006) Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444: 761-765. doi: 10.1038/nature05349
    [123] Buijs JT, Rentsch CA, van der Horst G, et al. (2007) BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol 171: 1047-1057. doi: 10.2353/ajpath.2007.070168
    [124] Bokobza SM, Ye L, Kynaston HG, et al. (2010) GDF‐9 promotes the growth of prostate cancer cells by protecting them from apoptosis. J Cell Physiol 225: 529-536. doi: 10.1002/jcp.22235
    [125] Bokobza SM, Ye L, Kynaston H, et al. (2011) Growth and differentiation factor 9 (GDF-9) induces epithelial–mesenchymal transition in prostate cancer cells. Mol Cell Biochem 349: 33-40. doi: 10.1007/s11010-010-0657-5
    [126] Yan C, Wang P, DeMayo J, et al. (2001) Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 15: 854-866. doi: 10.1210/mend.15.6.0662
    [127] Wu X, Matzuk MM (2002) GDF-9 and BMP-15: oocyte organizers. Rev Endocr Metab Disord 3: 27-32. doi: 10.1023/A:1012796601311
    [128] Peng J, Li Q, Wigglesworth K, et al. (2013) Growth differentiation factor 9: bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proc Natl Acad Sci U S A 110: E776-E785. doi: 10.1073/pnas.1218020110
    [129] Brown DA, Stephan C, Ward RL, et al. (2006) Measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improves prostate cancer diagnosis. Clin Cancer Res 12: 89-96. doi: 10.1158/1078-0432.CCR-05-1331
    [130] Aw Yong KM, Zeng Y, Vindivich D, et al. (2014) Morphological effects on expression of growth differentiation factor 15 (GDF15), a marker of metastasis. J Cell Physiol 229: 362-373. doi: 10.1002/jcp.24458
    [131] Kojima M, Troncoso P, Babaian RJ (1998) Influence of noncancerous prostatic tissue volume on prostate-specific antigen. Urology 51: 293-299. doi: 10.1016/S0090-4295(97)00497-4
    [132] Gritsman K, Talbot WS, Schier AF (2000) Nodal signaling patterns the organizer. Development 127: 921-932.
    [133] Gray PC, Harrison CA, Vale W (2003) Cripto forms a complex with activin and type II activin receptors and can block activin signaling. Proc Natl Acad Sci U S A 100: 5193-5198. doi: 10.1073/pnas.0531290100
    [134] Harrison CA, Gray PC, Vale WW, et al. (2005) Antagonists of activin signaling: mechanisms and potential biological applications. Trends Endocrinol Metab 16: 73-78. doi: 10.1016/j.tem.2005.01.003
    [135] Yeo C-Y, Whitman M (2001) Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Mol Cell 7: 949-957. doi: 10.1016/S1097-2765(01)00249-0
    [136] Chen C, Shen MM (2004) Two modes by which Lefty proteins inhibit nodal signaling. Curr Biol 14: 618-624. doi: 10.1016/j.cub.2004.02.042
    [137] Belo JA, Bachiller D, Agius E, et al. (2000) Cerberus-like is a secreted BMP and nodal antagonist not essential for mouse development. Genesis 26: 265-270.
    [138] Lawrence MG, Margaryan NV, Loessner D, et al. (2011) Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells. Prostate 71: 1198-1209. doi: 10.1002/pros.21335
    [139] De Silva T, Ye G, Liang Y-Y, et al. (2012) Nodal promotes glioblastoma cell growth. Frontiers Endocrinol 3: 1-6.
    [140] Aykul S, Ni W, Mutatu W, et al. (2014) Human cerberus prevents nodal-receptor binding, inhibits nodal signaling, and suppresses nodal-mediated phenotypes. PLoS One 10: e0114954.
    [141] Vo BT, Khan SA (2011) Expression of nodal and nodal receptors in prostate stem cells and prostate cancer cells: autocrine effects on cell proliferation and migration. Prostate 71: 1084-1096. doi: 10.1002/pros.21326
    [142] Yingling JM, Blanchard KL, Sawyer JS (2004) Development of TGF-β signalling inhibitors for cancer therapy. Nat Rev Drug Discov 3: 1011-1022. doi: 10.1038/nrd1580
    [143] Isaacs MJ, Kawakami Y, Allendorph GP, et al. (2010) Bone morphogenetic protein-2 and-6 heterodimer illustrates the nature of ligand-receptor assembly. Mol Endocrinol 24: 1469-1477. doi: 10.1210/me.2009-0496
    [144] Neugebauer JM, Kwon S, Kim H-S, et al. (2015) The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo. Proc Natl Acad Sci U S A 112: E2307-E2316. doi: 10.1073/pnas.1501449112
    [145] Yeo C-Y, Whitman M (2001) Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Mol Cell 7: 949-957. doi: 10.1016/S1097-2765(01)00249-0
    [146] Fuerer C, Nostro MC, Constam DB (2014) Nodal. Gdf1 heterodimers with bound prodomains enable serum-independent nodal signaling and endoderm differentiation. J Biol Chem 289: 17854-17871.
    [147] Harrington AE, Morris‐Triggs SA, Ruotolo BT, et al. (2006) Structural basis for the inhibition of activin signalling by follistatin. EMBO J 25: 1035-1045. doi: 10.1038/sj.emboj.7601000
    [148] Guo X, Wang X-F (2009) Signaling cross-talk between TGF-β/BMP and other pathways. Cell Res 19: 71-88. doi: 10.1038/cr.2008.302
  • Reader Comments
  • © 2017 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(7055) PDF downloads(1183) Cited by(2)

Article outline

Figures and Tables

Figures(3)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog