Gene Symbol: Smad7
Description: SMAD family member 7
Alias: CRCS3, MADH7, MADH8, mothers against decapentaplegic homolog 7, MAD (mothers against decapentaplegic, Drosophila) homolog 7, MAD homolog 8, Mothers against decapentaplegic, drosophila, homolog of, 7, SMAD, mothers against DPP homolog 7, hSMAD7, mothers against DPP homolog 8
Species: human
Products:     Smad7

Top Publications

  1. Tenesa A, Farrington S, Prendergast J, Porteous M, Walker M, Haq N, et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet. 2008;40:631-7 pubmed publisher
    ..008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology. ..
  2. Ekman M, Mu Y, Lee S, Edlund S, Kozakai T, Thakur N, et al. APC and Smad7 link TGF? type I receptors to the microtubule system to promote cell migration. Mol Biol Cell. 2012;23:2109-21 pubmed publisher
    ..However, the role of APC for cellular extension in response to extracellular signals is less clear. Smad7 is a direct target gene for transforming growth factor-? (TGF?) and is known to inhibit various TGF?-induced ..
  3. Yan X, Zhang J, Pan L, Wang P, Xue H, Zhang L, et al. TSC-22 promotes transforming growth factor ?-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity. Mol Cell Biol. 2011;31:3700-9 pubmed publisher
    ..Here we report that TSC-22 (TGF-?-stimulated clone 22) facilitates TGF-? signaling by antagonizing Smad7 activity to increase receptor stability...
  4. Hirata H, Hinoda Y, Nakajima K, Kikuno N, Yamamura S, Kawakami K, et al. Wnt antagonist gene polymorphisms and renal cancer. Cancer. 2009;115:4488-503 pubmed publisher
    ..protein 4 (sFRP4) (rs1802073 and rs1802074), mothers against decapentaplegic homolog (SMAD) family member 7 or SMAD7 (rs12953717), and disheveled associated activator of morphogenesis 2 or DAAM2 (rs6937133 and rs2504106) using ..
  5. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, et al. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001;276:12477-80 pubmed
    b>Smad7 is an inhibitory Smad that acts as a negative regulator of signaling by the transforming growth factor-beta (TGF-beta) superfamily proteins...
  6. Al Salihi M, Herhaus L, MacArtney T, Sapkota G. USP11 augments TGFβ signalling by deubiquitylating ALK5. Open Biol. 2012;2:120063 pubmed publisher
    The TGFβ receptors signal through phosphorylation and nuclear translocation of SMAD2/3. SMAD7, a transcriptional target of TGFβ signals, negatively regulates the TGFβ pathway by recruiting E3 ubiquitin ligases and targeting TGFβ ..
  7. Gutierrez Aguilar R, Benmezroua Y, Balkau B, Marre M, Helbecque N, Charpentier G, et al. Minor contribution of SMAD7 and KLF10 variants to genetic susceptibility of type 2 diabetes. Diabetes Metab. 2007;33:372-8 pubmed
    Transgenic mice over-expressing SMAD7 in pancreatic beta-cells develop type 2 diabetes (T2D)...
  8. Peters U, Hutter C, Hsu L, Schumacher F, Conti D, Carlson C, et al. Meta-analysis of new genome-wide association studies of colorectal cancer risk. Hum Genet. 2012;131:217-34 pubmed publisher
    ..03; combined p value 1.9 × 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer. ..
  9. Dowdy S, Mariani A, Janknecht R. HER2/Neu- and TAK1-mediated up-regulation of the transforming growth factor beta inhibitor Smad7 via the ETS protein ER81. J Biol Chem. 2003;278:44377-84 pubmed
    ..mutations in TGF-beta signaling components or enhanced expression of inhibitors of the TGF-beta pathway such as Smad7. In this report we show that the oncoprotein HER2/Neu is able to collaborate with the ETS transcription factor ..

More Information


  1. Boyer Arnold N, Korc M. Smad7 abrogates transforming growth factor-beta1-mediated growth inhibition in COLO-357 cells through functional inactivation of the retinoblastoma protein. J Biol Chem. 2005;280:21858-66 pubmed
    b>Smad7 is overexpressed in 50% of human pancreatic cancers...
  2. Hong S, Lim S, Li A, Lee C, Lee Y, Lee E, et al. Smad7 binds to the adaptors TAB2 and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2. Nat Immunol. 2007;8:504-13 pubmed
    ..Here we show that the TGF-beta-induced signaling protein Smad7 bound to TAB2 and TAB3, which are adaptors that link the kinase TAK1 to 'upstream' regulators in the ..
  3. Javelaud D, Delmas V, Moller M, Sextius P, Andre J, Menashi S, et al. Stable overexpression of Smad7 in human melanoma cells inhibits their tumorigenicity in vitro and in vivo. Oncogene. 2005;24:7624-9 pubmed
    ..This led us to investigate the effect of inhibitory Smad7 overexpression on melanoma cell behavior...
  4. Zhang S, Fei T, Zhang L, Zhang R, Chen F, Ning Y, et al. Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation. Mol Cell Biol. 2007;27:4488-99 pubmed
    b>Smad7 plays an essential role in the negative-feedback regulation of transforming growth factor beta (TGF-beta) signaling by inhibiting TGF-beta signaling at the receptor level...
  5. Hayashi H, Abdollah S, Qiu Y, Cai J, Xu Y, Grinnell B, et al. The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell. 1997;89:1165-73 pubmed
    ..Here we demonstrate that Smad7 is an inhibitor of TGFbeta signaling...
  6. Wrana J, Attisano L. The Smad pathway. Cytokine Growth Factor Rev. 2000;11:5-13 pubmed
    ..In addition, we will summarize recent findings on the role of Smads as transcriptional co-modulators. ..
  7. Li Q, Zou C, Zou C, Han Z, Xiao H, Wei H, et al. MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett. 2013;335:168-74 pubmed publisher
    ..Furthermore, bioinformatic predictions and experimental validation were used to identify Smad7 as a direct target of miR-25...
  8. Passarelli M, Coghill A, Hutter C, Zheng Y, Makar K, Potter J, et al. Common colorectal cancer risk variants in SMAD7 are associated with survival among prediagnostic nonsteroidal anti-inflammatory drug users: a population-based study of postmenopausal women. Genes Chromosomes Cancer. 2011;50:875-86 pubmed publisher
    Common single nucleotide polymorphisms (SNPs) in SMAD7 (18q21) have been linked to colorectal cancer (CRC) risk in genome-wide association studies, but little is known about their effects on survival...
  9. Grönroos E, Hellman U, Heldin C, Ericsson J. Control of Smad7 stability by competition between acetylation and ubiquitination. Mol Cell. 2002;10:483-93 pubmed
    Smad proteins regulate gene expression in response to TGFbeta signaling. Here we present evidence that Smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of Smad7 on two lysine residues in its N terminus...
  10. Hata A, Lagna G, Massague J, Hemmati Brivanlou A. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 1998;12:186-97 pubmed
    ..Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy. ..
  11. Monteleone G, Del Vecchio Blanco G, Monteleone I, Fina D, Caruso R, Gioia V, et al. Post-transcriptional regulation of Smad7 in the gut of patients with inflammatory bowel disease. Gastroenterology. 2005;129:1420-9 pubmed
    ..production because of increased intracellular expression of the endogenous inhibitor of TGF-beta1 signaling, Smad7. In this study, we examined the molecular mechanism underlying the induction of Smad7 in the human gut...
  12. Kavsak P, Rasmussen R, Causing C, Bonni S, Zhu H, Thomsen G, et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 2000;6:1365-75 pubmed
    ..Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where ..
  13. Xiong F, Wu C, Bi X, Yu D, Huang L, Xu J, et al. Risk of genome-wide association study-identified genetic variants for colorectal cancer in a Chinese population. Cancer Epidemiol Biomarkers Prev. 2010;19:1855-61 pubmed publisher
    ..Our results provide new insights into colorectal tumorigenesis and have potential implications in early detection and target treatment of CRC in non-Western populations. ..
  14. Itoh F, Asao H, Sugamura K, Heldin C, ten Dijke P, Itoh S. Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads. EMBO J. 2001;20:4132-42 pubmed
    Inhibitory Smads, i.e. Smad6 and Smad7, are potent antagonists of the BMP-Smad pathway by interacting with activated bone morphogenetic protein (BMP) type I receptors and thereby preventing the activation of receptor-regulated Smads, or ..
  15. Lallemand F, Seo S, Ferrand N, Pessah M, L Hoste S, Rawadi G, et al. AIP4 restricts transforming growth factor-beta signaling through a ubiquitination-independent mechanism. J Biol Chem. 2005;280:27645-53 pubmed
    b>Smad7 functions as an intracellular antagonist in transforming growth factor-beta (TGF-beta) signaling...
  16. Wang H, Song K, Krebs T, Yang J, Danielpour D. Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55. Oncogene. 2008;27:6791-805 pubmed publisher
    ..We now show that Hic-5 can also control TGF-beta responses through an alternative mechanism involving Smad7, a key negative regulator of TGF-beta signaling. Hic-5 binds directly to Smad7...
  17. Morén A, Imamura T, Miyazono K, Heldin C, Moustakas A. Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases. J Biol Chem. 2005;280:22115-23 pubmed
    ..which otherwise cannot directly bind to Smad4, mediated poly-ubiquitination of Smad4 in the presence of Smad6 or Smad7. Smad4 co-localized with Smad7 and Smurf1 primarily in the cytoplasm and in peripheral cell protrusions...
  18. Liu W, Rui H, Wang J, Lin S, He Y, Chen M, et al. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 2006;25:1646-58 pubmed
    ..Here, we show that Axin activates TGF-beta signaling by forming a multimeric complex consisting of Smad7 and ubiquitin E3 ligase Arkadia...
  19. Osawa H, Nakajima M, Kato H, Fukuchi M, Kuwano H. Prognostic value of the expression of Smad6 and Smad7, as inhibitory Smads of the TGF-beta superfamily, in esophageal squamous cell carcinoma. Anticancer Res. 2004;24:3703-9 pubmed
    ..The expression of Smad6 and Smad7 as negative regulators was examined, to investigate the further effects of TGF-B superfamily signaling...
  20. Thompson C, Plummer S, Acheson L, Tucker T, Casey G, Li L. Association of common genetic variants in SMAD7 and risk of colon cancer. Carcinogenesis. 2009;30:982-6 pubmed publisher
    Two recent genome-wide association studies (GWAS) identified three common variants in SMAD7 (rs4464148, rs4939827 and rs12953717) that confer modest susceptibility to colorectal cancer...
  21. Slattery M, Herrick J, Curtin K, Samowitz W, Wolff R, Caan B, et al. Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. Cancer Res. 2010;70:1479-85 pubmed publisher
    Genome-wide association studies (GWAS) have identified SMAD7 on 8q21 as being associated with colorectal cancer...
  22. Mochizuki T, Miyazaki H, Hara T, Furuya T, Imamura T, Watabe T, et al. Roles for the MH2 domain of Smad7 in the specific inhibition of transforming growth factor-beta superfamily signaling. J Biol Chem. 2004;279:31568-74 pubmed
    ..b>Smad7 inhibits signaling by both TGF-beta and bone morphogenetic proteins (BMPs), whereas Smad6 inhibits TGF-beta ..
  23. Chen Q, Chen H, Zheng D, Kuang C, Fang H, Zou B, et al. Smad7 is required for the development and function of the heart. J Biol Chem. 2009;284:292-300 pubmed publisher
    ..These effects are largely mediated by Smad proteins. Smad7 is a negative regulator for the signaling of TGF-beta family members...
  24. Leng A, Liu T, He Y, Li Q, Zhang G. Smad4/Smad7 balance: a role of tumorigenesis in gastric cancer. Exp Mol Pathol. 2009;87:48-53 pubmed publisher
    ..K., Rachakonda, G., Deane, N.G., Datta, P.K., 2008. Smad7 induces hepatic metastasis in colorectal cancer. Br. J. Cancer 99, 957-965)...
  25. Yan X, Liu Z, Chen Y. Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin (Shanghai). 2009;41:263-72 pubmed
    ..The signaling of TGF-beta is finely regulated at different levels. Inhibitory Smads, including Smad6 and Smad7, are key regulators of TGF-beta/bone morphogenetic protein (BMP) signaling by negative feedback loops...
  26. Gulubova M, Manolova I, Ananiev J, Julianov A, Yovchev Y, Peeva K. Role of TGF-beta1, its receptor TGFbetaRII, and Smad proteins in the progression of colorectal cancer. Int J Colorectal Dis. 2010;25:591-9 pubmed publisher, we investigated the expression of TGF-beta1, its receptor TGFbetaRII, and the signaling proteins Smad4 and Smad7 in colorectal cancer tissue in relation to infiltration with antigen-presenting cells and some clinical and ..
  27. von Holst S, Picelli S, Edler D, Lenander C, Dalen J, Hjern F, et al. Association studies on 11 published colorectal cancer risk loci. Br J Cancer. 2010;103:575-80 pubmed publisher
    ..Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations. ..
  28. Kim S, Han J, Lee S, Koo M, Cho D, Bae S, et al. Smad7 acts as a negative regulator of the epidermal growth factor (EGF) signaling pathway in breast cancer cells. Cancer Lett. 2012;314:147-54 pubmed publisher
    Although it has been suggested that smad7 blocks downstream signaling of TGF-?, the role of smad7 in the EGF signaling pathway has not been fully elucidated...
  29. Song Q, Zhu B, Hu W, Cheng L, Gong H, Xu B, et al. A common SMAD7 variant is associated with risk of colorectal cancer: evidence from a case-control study and a meta-analysis. PLoS ONE. 2012;7:e33318 pubmed publisher
    A common genetic variant, rs4939827, located in SMAD7, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC)...
  30. Wang J, Zhao J, Chu E, Mok M, Go M, Man K, et al. Inhibitory role of Smad7 in hepatocarcinogenesis in mice and in vitro. J Pathol. 2013;230:441-52 pubmed publisher
    b>Smad7 is a principal inhibitor of the TGF?-Smad signalling pathway. We have investigated the functional significance of Smad7 in hepatocellular carcinoma (HCC)...
  31. Stolfi C, de Simone V, Colantoni A, Franzè E, Ribichini E, Fantini M, et al. A functional role for Smad7 in sustaining colon cancer cell growth and survival. Cell Death Dis. 2014;5:e1073 pubmed publisher
    ..factor (TGF)-? mainly owing to its ability to bind TGF-? receptor type I and abrogate TGF-?-driven signaling, Smad7 can interact with additional intracellular proteins and regulate TGF-?-independent pathways, thus having a key ..
  32. Chong P, Lin H, Wrana J, Forman Kay J. An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2. J Biol Chem. 2006;281:17069-75 pubmed
    ..Recognition of the receptors by Smurf2 is accomplished through an intermediary protein, Smad7. Here we have demonstrated that the WW3 domain of Smurf2 can directly bind to the Smad7 polyproline-tyrosine (PY) ..
  33. Grau A, Datta P, Zi J, Halder S, Beauchamp R. Role of Smad proteins in the regulation of NF-kappaB by TGF-beta in colon cancer cells. Cell Signal. 2006;18:1041-50 pubmed
    ..fails to activate NF-kappaB or phosphorylate IkappaB-alpha in FET-1 cells expressing the inhibitory Smad, Smad7. Taken together, these results suggest a role for Smad4 in the transcriptional activation of NF-kappaB, and a ..
  34. Massague J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753-91 pubmed
    ..Mutations in these pathways are the cause of various forms of human cancer and developmental disorders. ..
  35. Seo S, Lallemand F, Ferrand N, Pessah M, L Hoste S, Camonis J, et al. The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation. EMBO J. 2004;23:3780-92 pubmed
    ..Tiul1 associates constitutively with Smad7 and induces degradation of the activated type I receptor without affecting the expression levels of Smad7...
  36. Komuro A, Imamura T, Saitoh M, Yoshida Y, Yamori T, Miyazono K, et al. Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1). Oncogene. 2004;23:6914-23 pubmed
    b>Smad7 negatively regulates transforming growth factor (TGF)-beta superfamily signaling by binding to activated type I receptors, thereby preventing the phosphorylation of receptor-regulated Smads (R-Smads), as well as by recruiting HECT-..
  37. Shi W, Sun C, He B, Xiong W, Shi X, Yao D, et al. GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J Cell Biol. 2004;164:291-300 pubmed
    ..Reversible phosphorylation regulates fundamental aspects of cell activity. TGFbeta-induced Smad7 binds to type I receptor (TGFbeta type I receptor; TbetaRI) functioning as a receptor kinase antagonist...
  38. Edlund S, Landström M, Heldin C, Aspenstrom P. Smad7 is required for TGF-beta-induced activation of the small GTPase Cdc42. J Cell Sci. 2004;117:1835-47 pubmed
    ..The inhibitory Smads, Smad6 and Smad7, are considered to function as negative regulators of the TGF-beta/Smad signaling cascade...
  39. Monteleone G, Del Vecchio Blanco G, Palmieri G, Vavassori P, Monteleone I, Colantoni A, et al. Induction and regulation of Smad7 in the gastric mucosa of patients with Helicobacter pylori infection. Gastroenterology. 2004;126:674-82 pubmed
    ..Induction of Smad7 by interferon (IFN)-gamma was examined in normal gastric mucosal biopsy specimens, whereas the effect of Smad7 ..
  40. Gibson L, Johnson N, Fraser A, dos Santos Silva I, Houlston R, Peto J, et al. No breast cancer association for transforming growth factor-beta pathway colorectal cancer single nucleotide polymorphisms. Cancer Epidemiol Biomarkers Prev. 2009;18:1934-6 pubmed publisher
    b>SMAD7 and GREM1 are signaling components on the transforming growth factor-beta pathway, which regulates normal mammary gland development and has been implicated in breast tumor invasion and metastasis...
  41. Topper J, Cai J, Qiu Y, Anderson K, Xu Y, Deeds J, et al. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc Natl Acad Sci U S A. 1997;94:9314-9 pubmed
    ..Utilizing a differential display approach, we have identified two genes, Smad6 and Smad7, encoding members of the MAD-related family of molecules, selectively induced in cultured human vascular ..
  42. Niittymäki I, Kaasinen E, Tuupanen S, Karhu A, Jarvinen H, Mecklin J, et al. Low-penetrance susceptibility variants in familial colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2010;19:1478-83 pubmed publisher
    ..Our results emphasize the need to characterize the remaining molecular basis of familial CRC, which should eventually yield in individualized targeting of preventive interventions. ..
  43. Kim Y, Lee H, Lee H, Hur K, Kim W, Bang Y, et al. Prognostic significance of the expression of Smad4 and Smad7 in human gastric carcinomas. Ann Oncol. 2004;15:574-80 pubmed
    ..profiles and the patient's survival, the expression of common mediator Smad (Smad4) and inhibitory Smad (Smad7) were evaluated immunohistochemically in 304 consecutive gastric carcinomas using the tissue array method...
  44. Loh Y, Mitrou P, Wood A, Luben R, McTaggart A, Khaw K, et al. SMAD7 and MGMT genotype variants and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study. Cancer Epidemiol. 2011;35:369-74 pubmed publisher
    The SMAD7 gene was recently identified to be associated with colorectal cancer risk. Smad7 protein is a known inhibitor of TGF-? signalling pathway which has a prominent role in tumorigenesis...
  45. Rizzo A, Waldner M, Stolfi C, Sarra M, Fina D, Becker C, et al. Smad7 expression in T cells prevents colitis-associated cancer. Cancer Res. 2011;71:7423-32 pubmed publisher
    ..In this study, we investigated the role of the TGF? signaling inhibitor Smad7 in CAC pathogenesis...
  46. Theohari I, Giannopoulou I, Magkou C, Nomikos A, Melissaris S, Nakopoulou L. Differential effect of the expression of TGF-? pathway inhibitors, Smad-7 and Ski, on invasive breast carcinomas: relation to biologic behavior. APMIS. 2012;120:92-100 pubmed publisher
    ..Smad-7 appears to be related with an aggressive phenotype, whereas Ski expression is related to a less aggressive behavior and positively influences patients' survival. ..
  47. Miyazono K. TGF-beta signaling by Smad proteins. Cytokine Growth Factor Rev. 2000;11:15-22 pubmed
    ..Through interaction with different transcription factors and transcriptional co-activators or co-repressors, Smads may exhibit specific effects in various cell types. ..
  48. Aragon E, Goerner N, Xi Q, Gomes T, Gao S, Massague J, et al. Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-? Pathways. Structure. 2012;20:1726-36 pubmed publisher
    ..growth factor (TGF)-? and BMP signaling is mediated by Smads 1-5 (R-Smads and Co-Smads) and inhibited by Smad7, a major hub of regulation of TGF-? and BMP receptors by negative feedback and antagonistic signals...
  49. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian J, Heuchel R, et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 1997;389:631-5 pubmed
    ..Here we report the identification of Smad7, which is related to Smad6...
  50. Javelaud D, Mohammad K, McKenna C, Fournier P, Luciani F, Niewolna M, et al. Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Res. 2007;67:2317-24 pubmed
    ..1205Lu melanoma cells, stably transfected to overexpress the natural TGF-beta/Smad signaling inhibitor Smad7, were studied in an experimental model of bone metastasis whereby tumor cells are inoculated into the left cardiac ..
  51. Nagano Y, Mavrakis K, Lee K, Fujii T, Koinuma D, Sase H, et al. Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling. J Biol Chem. 2007;282:20492-501 pubmed
    ..Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly through targeting the signaling receptors, whereas SnoN and c-Ski repress ..
  52. Broderick P, Sellick G, Fielding S, Catovsky D, Houlston R. Lack of a relationship between the common 18q24 variant rs12953717 and risk of chronic lymphocytic leukemia. Leuk Lymphoma. 2008;49:271-2 pubmed publisher
    ..18q24 harbors mothers against decapentaplegic homolog 7 (SMAD7), an intracellular antagonist of TGF-beta signaling which participates in a negative ..
  53. Tomlinson I, Webb E, Carvajal Carmona L, Broderick P, Howarth K, Pittman A, et al. A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet. 2008;40:623-30 pubmed publisher
    ..3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition. ..
  54. Tang Y, Liu Z, Zhao L, Clemens T, Cao X. Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion. J Biol Chem. 2008;283:23956-63 pubmed publisher
    ..Here we show that Smad7 promotes cell-cell adhesion by stabilizing beta-catenin and consequently increases the beta-catenin-E-cadherin ..
  55. Ibarrola N, Kratchmarova I, Nakajima D, Schiemann W, Moustakas A, Pandey A, et al. Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor beta signaling. BMC Cell Biol. 2004;5:2 pubmed
    ..Coimmunoprecipitation studies indicated that Smad7 and Smad2, but not Smad3 or 4, interact with AMSH-2...
  56. Ogunjimi A, Briant D, Pece Barbara N, Le Roy C, Di Guglielmo G, Kavsak P, et al. Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain. Mol Cell. 2005;19:297-308 pubmed
    ..In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor ..
  57. Peters U, Jiao S, Schumacher F, Hutter C, Aragaki A, Baron J, et al. Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis. Gastroenterology. 2013;144:799-807.e24 pubmed publisher
    ..The roles of these genes and their products in cancer pathogenesis warrant further investigation. ..
  58. Wicks S, Haros K, Maillard M, Song L, Cohen R, Dijke P, et al. The deubiquitinating enzyme UCH37 interacts with Smads and regulates TGF-beta signalling. Oncogene. 2005;24:8080-4 pubmed
    ..In GST pull down experiments, UCH37 bound weakly to Smad2 and Smad3, and bound very strongly to Smad7 in a region that is distinct from the -PY- motif in Smad7 that interacts with Smurf ubiquitin ligases...
  59. Broderick P, Carvajal Carmona L, Pittman A, Webb E, Howarth K, Rowan A, et al. A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nat Genet. 2007;39:1315-7 pubmed
    ..selected SNPs in three replication sample sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF-beta and Wnt signaling) associated with CRC...
  60. Edlund S, Bu S, Schuster N, Aspenstrom P, Heuchel R, Heldin N, et al. Transforming growth factor-beta1 (TGF-beta)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated protein kinase kinase 3. Mol Biol Cell. 2003;14:529-44 pubmed
    The inhibitory Smad7, a direct target gene for transforming growth factor-beta (TGF-beta), mediates TGF-beta1-induced apoptosis in several cell types...
  61. Smith A, Iwanaga R, Drasin D, Micalizzi D, Vartuli R, Tan A, et al. The miR-106b-25 cluster targets Smad7, activates TGF-? signaling, and induces EMT and tumor initiating cell characteristics downstream of Six1 in human breast cancer. Oncogene. 2012;31:5162-71 pubmed publisher
    ..p21 and BIM, we demonstrate for the first time that this same cluster can additionally target the inhibitory Smad7 protein, resulting in increased levels of the TGF-? type I receptor and downstream activation of TGF-? signaling...
  62. Pittman A, Naranjo S, Webb E, Broderick P, Lips E, van Wezel T, et al. The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression. Genome Res. 2009;19:987-93 pubmed publisher
    Recent genome-wide scans for colorectal cancer (CRC) have revealed the SMAD7 (mothers against decapentaplegic homolog 7) gene as a locus associated with a modest, but highly significant increase in CRC risk...
  63. Li X, YANG X, Hu N, Sun J, LI F, Li M. A risk-associated single nucleotide polymorphism of SMAD7 is common to colorectal, gastric, and lung cancers in a Han Chinese population. Mol Biol Rep. 2011;38:5093-7 pubmed publisher
    b>SMAD7 has been demonstrated to antagonize TGF-?-mediated fibrosis, carcinogenesis, and inflammation...
  64. Kamiya Y, Miyazono K, Miyazawa K. Smad7 inhibits transforming growth factor-beta family type i receptors through two distinct modes of interaction. J Biol Chem. 2010;285:30804-13 pubmed publisher
    The inhibitory Smads (I-Smads), i.e. Smad6 and Smad7, are negative regulators of transforming growth factor-? (TGF-?) family signaling...
  65. Kopp J, Preis E, Said H, Hafemann B, Wickert L, Gressner A, et al. Abrogation of transforming growth factor-beta signaling by SMAD7 inhibits collagen gel contraction of human dermal fibroblasts. J Biol Chem. 2005;280:21570-6 pubmed
    ..In an attempt to intervene in profibrogenic TGF-beta functions, ectopic expression of Smad7 or dominant negative Smads3/4 completely inhibited contractility of scar-derived and normal fibroblasts after ..
  66. Hariharan R, Babu J, P R, Pillai M. Mutational analysis of Smad7 in human cervical cancer. Oncol Rep. 2009;21:1001-4 pubmed
    Our aim was to carry out mutational analysis of Smad7 exon 4 that codes for the Smad7 MH2 domain in human cervical cancer tissues...
  67. Davoodpour P, Landström M. 2-Methoxyestradiol-induced apoptosis in prostate cancer cells requires Smad7. J Biol Chem. 2005;280:14773-9 pubmed
    ..Here we report that the expression of Smad7, an adaptor molecule required to activate p38 MAPK in the transforming growth factor beta signaling pathway, is ..
  68. Middeldorp A, Jagmohan Changur S, van Eijk R, Tops C, Devilee P, Vasen H, et al. Enrichment of low penetrance susceptibility loci in a Dutch familial colorectal cancer cohort. Cancer Epidemiol Biomarkers Prev. 2009;18:3062-7 pubmed publisher
    ..Overall, our results suggest that clustering of low-risk variants may explain part of the excess risk in CRC families. ..
  69. Kuratomi G, Komuro A, Goto K, Shinozaki M, Miyazawa K, Miyazono K, et al. NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor. Biochem J. 2005;386:461-70 pubmed
    Inhibitory Smad, Smad7, is a potent inhibitor of TGF-beta (transforming growth factor-beta) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads)...
  70. Kim B, Lee H, Park S, Lee S, Karpova T, McNally J, et al. Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation. Mol Cell Biol. 2004;24:2251-62 pubmed
    b>Smad7 inhibits responses mediated by transforming growth factor beta (TGF-beta) and acts in a negative-feedback loop to regulate the intensity or duration of the TGF-beta signal...
  71. Kersten C, Sivertsen E, Hystad M, Forfang L, Smeland E, Myklebust J. BMP-6 inhibits growth of mature human B cells; induction of Smad phosphorylation and upregulation of Id1. BMC Immunol. 2005;6:9 pubmed
    ..Furthermore, B cells were demonstrated to upregulate BMP-6 mRNA upon stimulation with anti-IgM. In mature human B cells, BMP-6 inhibited cell growth, and rapidly induced phosphorylation of Smad1/5/8 followed by an upregulation of Id1. ..
  72. Eichhorn P, Rodón L, Gonzàlez Juncà A, Dirac A, Gili M, Martínez Sáez E, et al. USP15 stabilizes TGF-? receptor I and promotes oncogenesis through the activation of TGF-? signaling in glioblastoma. Nat Med. 2012;18:429-35 pubmed publisher
    ..USP15 binds to the SMAD7-SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) complex and deubiquitinates and stabilizes type I TGF-? ..
  73. Edlund S, Lee S, Grimsby S, Zhang S, Aspenstrom P, Heldin C, et al. Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis. Mol Cell Biol. 2005;25:1475-88 pubmed
    ..Here we report that Smad7 interacts with beta-catenin and lymphoid enhancer binding factor 1/T-cell-specific factor (LEF1/TCF), ..
  74. Dowdy S, Mariani A, Reinholz M, Keeney G, Spelsberg T, Podratz K, et al. Overexpression of the TGF-beta antagonist Smad7 in endometrial cancer. Gynecol Oncol. 2005;96:368-73 pubmed
    We have shown that HER2/Neu may activate the Smad7 promoter in endometrial, ovarian, and breast cancer cell lines...
  75. Halder S, Beauchamp R, Datta P. Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. Exp Cell Res. 2005;307:231-46 pubmed
    ..The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in ..
  76. Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, et al. Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 2003;22:6458-70 pubmed
    ..Arkadia physically interacts with inhibitory Smad, Smad7, and induces its poly-ubiquitination and degradation...